The human immune response to respiratory syncytial virus infection

Clinical Microbiology Reviews

Volumn 30, Issue 2, 2017, Pages 481-502

  Russell, Clark D ^a   Unger, Stefan A ^b   Walton, Marc ^a   Schwarze, Jürgen ^a,b  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

Immunology; Respiratory syncytial virus

Indexed keywords

AZATHIOPRINE; CATHELICIDIN; CD11B ANTIGEN; CD18 ANTIGEN; CD3 ANTIGEN; CD4 ANTIGEN; CD40 ANTIGEN; CD8 ANTIGEN; CD94 ANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; EOSINOPHIL CATIONIC PROTEIN; FAS ANTIGEN; GAMMA INTERFERON; IMMUNOGLOBULIN A; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 10; INTERLEUKIN 13; INTERLEUKIN 1BETA; INTERLEUKIN 2; INTERLEUKIN 6; INTERLEUKIN 8; LIPOCORTIN 5; LYMPHOCYTE FUNCTION ASSOCIATED ANTIGEN 1; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MYCOPHENOLATE MOFETIL; RANTES; TUMOR NECROSIS FACTOR; UNINDEXED DRUG; CYTOKINE;

BRONCHIOLITIS; CD8+ T LYMPHOCYTE; CELL DIFFERENTIATION; DISEASE SEVERITY; FORCED EXPIRATORY VOLUME; HUMAN; HYPOXIA; IMMUNE RESPONSE; IMMUNOPATHOGENESIS; LUNG LAVAGE; NEUTROPHIL COUNT; NONHUMAN; PROTEIN EXPRESSION; RESPIRATORY SYNCYTIAL VIRUS INFECTION; REVIEW; TH1 TH2 BALANCE; VIRAL CLEARANCE; VIRUS LOAD; HUMAN RESPIRATORY SYNCYTIAL VIRUS; IMMUNOLOGY; T LYMPHOCYTE;

CYTOKINES; HUMANS; RESPIRATORY SYNCYTIAL VIRUS INFECTIONS; RESPIRATORY SYNCYTIAL VIRUSES; T-LYMPHOCYTES;

EID: 85012113486     PISSN: 08938512     EISSN: 10986618     Source Type: Journal    
DOI: 10.1128/CMR.00090-16     Document Type: Review

References (186)

1. Smith PK, Wang SZ, Dowling KD, Forsyth KD. 2001. Leucocyte populations in respiratory syncytial virus-induced bronchiolitis. J Paediatr Child Health 37:146-151. https://doi.org/10.1046/j.1440-1754.2001.00618.x.
2. O'Donnell DR, Carrington D. 2002. Peripheral blood lymphopenia and neutrophilia in children with severe respiratory syncytial virus disease. Pediatr Pulmonol 34:128-130. https://doi.org/10.1002/ppul.10140.
3. Welliver TP, Garofalo RP, Hosakote Y, Hintz KH, Avendano L, Sanchez K, Velozo L, Jafri H, Chavez-Bueno S, Ogra PL, McKinney L, Reed JL, Welliver RC. 2007. Severe human lower respiratory tract illness caused by respiratory syncytial virus and influenza virus is characterized by the absence of pulmonary cytotoxic lymphocyte responses. J Infect Dis 195:1126-1136. https://doi.org/10.1086/512615.
4. Heidema J, Lukens MV, van Maren WWC, van Dijk MEA, Otten HG, van Vught AJ, van der Werff DBM, van Gestel SJP, Semple MG, Smyth RL, Kimpen JLL, van Bleek GM. 2007. CD8(_) T cell responses in bronchoalveolar lavage fluid and peripheral blood mononuclear cells of infants with severe primary respiratory syncytial virus infections. J Immunol 179:8410-8417. https://doi.org/10.4049/jimmunol.179.12.8410.
5. Everard ML, Swarbrick A, Wrightham M, McIntyre J, Dunkley C, James PD, Sewell HF, Milner AD. 1994. Analysis of cells obtained by bronchial lavage of infants with respiratory syncytial virus infection. Arch Dis Child 71:428-432. https://doi.org/10.1136/adc.71.5.428.
6. Emboriadou M, Hatzistilianou M, Magnisali C, Sakelaropoulou A, Exintari M, Conti P, Aivazis V. 2007. Human neutrophil elastase in RSV bronchiolitis. Ann Clin Lab Sci 37:79-84.
7. Abu-Harb M, Bell F, Finn A, Rao WH, Nixon L, Shale D, Everard ML. 1999. IL-8 and neutrophil elastase levels in the respiratory tract of infants with RSV bronchiolitis. Eur Respir J 14:139-143. https://doi.org/10.1034/j.1399-3003.1999.14a23.x.
8. Wang SZ, Smith PK, Lovejoy M, Bowden JJ, Alpers JH, Forsyth KD. 1998. The apoptosis of neutrophils is accelerated in respiratory syncytial virus (RSV)-induced bronchiolitis. Clin Exp Immunol 114:49-54. https://doi.org/10.1046/j.1365-2249.1998.00681.x.
9. Wang SZ, Smith PK, Lovejoy M, Bowden JJ, Alpers JH, Forsyth KD. 1998. Shedding of L-selectin and PECAM-1 and upregulation of Mac-1 and ICAM-1 on neutrophils in RSV bronchiolitis. Am J Physiol 275:L983-L989.
10. Lukens MV, van de Pol AC, Coenjaerts FEJ, Jansen NJG, Kamp VM, Kimpen JLL, Rossen JWA, Ulfman LH, Tacke CEA, Viveen MC, Koenderman L, Wolfs TFW, van Bleek GM. 2010. A systemic neutrophil response precedes robust CD8_ T-cell activation during natural respiratory syncytial virus infection in infants. J Virol 84:2374-2383. https://doi.org/10.1128/JVI.01807-09.
11. Johnson JE, Gonzales RA, Olson SJ, Wright PF, Graham BS. 2007. The histopathology of fatal untreated human respiratory syncytial virus infection. Modern Pathol 20:108-119. https://doi.org/10.1038/modpathol.3800725.
12. Halfhide CP, Flanagan BF, Brearey SP, Hunt JA, Fonceca AM, McNamara PS, Howarth D, Edwards S, Smyth RL. 2011. Respiratory syncytial virus binds and undergoes transcription in neutrophils from the blood and airways of infants with severe bronchiolitis. J Infect Dis 204:451-458. https://doi.org/10.1093/infdis/jir280.
13. Yui I, Hoshi A, Shigeta Y, Takami T, Nakayama T. 2003. Detection of human respiratory syncytial virus sequences in peripheral blood mononuclear cells. J Med Virol 70:481-489. https://doi.org/10.1002/jmv.10421.
14. Cortjens B, de Boer OJ, de Jong R, Antonis AFG, Pineros YSS, Lutter R, van Woensel JBM, Bem RA. 2016. Neutrophil extracellular traps cause airway obstruction during respiratory syncytial virus disease. J Pathol 238:401-411. https://doi.org/10.1002/path.4660.
15. Larranaga CL, Ampuero SL, Luchsinger VF, Carrion FA, Aguilar NV, Morales PR, Palomino MAM, Tapia LF, Avendano LF. 2009. Impaired immune response in severe human lower tract respiratory infection by respiratory syncytial virus. Pediatr Infect Dis J 28:867-873. https://doi.org/10.1097/INF.0b013e3181a3ea71.
16. De Weerd W, Twilhaar WN, Kimpen JL. 1998. T cell subset analysis in peripheral blood of children with RSV bronchiolitis. Scand J Infect Dis 30:77-80. https://doi.org/10.1080/003655498750002349.
17. Noyola DE, Juarez-Vega G, Monjaras-Avila C, Escalante-Padron F, Rangel-Ramirez V, Cadena-Mota S, Monsivais-Urenda A, Garcia-Sepulveda CA, Gonzalez-Amaro R. 2015. NK cell immunophenotypic and genotypic analysis of infants with severe respiratory syncytial virus infection. Microbiol Immunol 59:389-397. https://doi.org/10.1111/1348-0421.12265.
18. Brand HK, Ferwerda G, Preijers F, de Groot R, Neeleman C, Staal FJT, Warris A, Hermans PWM. 2013. CD4(+)T-cell counts and interleukin-8 and CCL-5 plasma concentrations discriminate disease severity in children with RSV infection. Pediatric Res 73:187-193. https://doi.org/10.1038/pr.2012.163.
19. Brand HK, Ahout IML, de Ridder D, van Diepen A, Li Y, Zaalberg M, Andeweg A, Roeleveld N, de Groot R, Warris A, Hermans PWM, Ferwerda G, Staal FJT. 2015. Olfactomedin 4 serves as a marker for disease severity in pediatric respiratory syncytial virus (RSV) infection. PLoS One 10:e0131927. https://doi.org/10.1371/journal.pone.0131927.
20. Kerrin A, Fitch P, Errington C, Kerr D, Waxman L, Riding K, McCormack J, Mehendele F, McSorley H, MacKenzie K, Wronski S, Braun A, Levin R, Theilen U, Schwarze J. 16 August 2016. Differential lower airway dendritic cell patterns may reveal distinct endotypes of RSV bronchiolitis. Thorax https://doi.org/10.1136/thoraxjnl-2015-207358.
21. Bem RA, Bos AP, Bots M, Wolbink AM, Van Ham SM, Medema JP, Lutter R, Van Woensel JBM. 2008. Activation of the granzyme pathway in children with severe respiratory syncytial virus infection. Pediatric Res 63:650-655. https://doi.org/10.1203/PDR.0b013e31816fdc32.
22. Gill MA, Long K, Kwon T, Muniz L, Mejias A, Connolly J, Roy L, Banchereau J, Ramilo O. 2008. Differential recruitment of dendritic cells and monocytes to respiratory mucosal sites in children with influenza virus or respiratory syncytial virus infection. J Infect Dis 198:1667-1676. https://doi.org/10.1086/593018.
23. Gill MA, Palucka AK, Barton T, Ghaffar F, Jafri H, Banchereau J, Ramilo O. 2005. Mobilization of plasmacytoid and myeloid dendritic cells to mucosal sites in children with respiratory syncytial virus and other viral respiratory infections. J Infect Dis 191:1105-1115. https://doi.org/10.1086/428589.
24. Weng KZ, Zhang JX, Mei XQ, Wu A, Zhang BZ, Cai MY, Zheng YH, Ke ZY. 2014. Lower number of plasmacytoid dendritic cells in peripheral blood of children with bronchiolitis following respiratory syncytial virus in-fection. Influenza Other Respir Viruses 8:469-473. https://doi.org/10.1111/irv.12242.
25. Midulla F, Villani A, Panuska JR, Dab I, Kolls JK, Merolla R, Ronchetti R. 1993. Respiratory syncytial virus lung infection in infants: immunoregulatory role of infected alveolar macrophages. J Infect Dis 168: 1515-1519. https://doi.org/10.1093/infdis/168.6.1515.
26. Panuska JR, Hertz MI, Taraf H, Villani A, Cirino NM. 1992. Respiratory syncytial virus infection of alveolar macrophages in adult transplant patients. Am Rev Respir Dis 145:934-939. https://doi.org/10.1164/ajrccm/145.4_Pt_1.934.
27. Bendelja K, Vojvoda V, Aberle N, Cepin-Bogovic J, Gagro A, Mlinaric-Galinovic G, Rabatic S. 2010. Decreased Toll-like receptor 8 expression and lower TNF-alpha synthesis in infants with acute RSV infection. Respir Res 11:143. https://doi.org/10.1186/1465-9921-11-143.
28. Gagro A, Tominac M, Krsulovic-Hresic V, Bace A, Matic M, Drazenovic V, Mlinaric-Galinovic G, Kosor E, Gotovac K, Bolanca I, Batinica S, Rabatic S. 2004. Increased Toll-like receptor 4 expression in infants with respiratory syncytial virus bronchiolitis. Clin Exp Immunol 135:267-272. https://doi.org/10.1111/j.1365-2249.2004.02364.x.
29. Lindemans CA, Kimpen JLL, Luijk B, Heidema J, Kanters D, van der Ent CK, Koenderman L. 2006. Systemic eosinophil response induced by respiratory syncytial virus. Clin Exp Immunol 144:409-417. https://doi.org/10.1111/j.1365-2249.2006.03084.x.
30. Kawasaki Y, Hosoya M, Kanno H, Suzuki H. 2006. Serum regulated upon activation, normal T cell expressed and presumably secreted concentrations and eosinophils in respiratory syncytial virus infection. Pediatrics Int 48:257-260. https://doi.org/10.1111/j.1442-200X.2006.02199.x.
31. Dimova-Yaneva D, Russell D, Main M, Brooker RJ, Helms PJ. 2004. Eosinophil activation and cysteinyl leukotriene production in infants with respiratory syncytial virus bronchiolitis. Clin Exp Allergy 34: 555-558. https://doi.org/10.1111/j.1365-2222.2004.1918.x.
32. Kim HH, Lee MH, Lee JS. 2007. Eosinophil cationic protein and chemokines in nasopharyngeal secretions of infants with respiratory syncytial virus (RSV) bronchiolitis and non-RSV bronchiolitis. J Korean Med Sci 22:37-42.
33. Harrison AM, Bonville CA, Rosenberg HF, Domachowske JB. 1999. Respiratory syncytical virus-induced chemokine expression in the lower airways: eosinophil recruitment and degranulation. Am J Respir Crit Care Med 159:1918-1924. https://doi.org/10.1164/ajrccm.159.6.9805083.
34. Park JS, Kim YH, Kwon E, Callaway Z, Fujisawa T, Kim CK. 2015. Different inflammatory mechanisms of human metapneumovirus and respiratory syncytial virus. J Allergy Clin Immunol 135:AB150.
35. Garofalo R, Kimpen JL, Welliver RC, Ogra PL. 1992. Eosinophil degranulation in the respiratory tract during naturally acquired respiratory syncytial virus infection. J Pediatr 120:28-32. https://doi.org/10.1016/S0022-3476(05)80592-X.
36. Volovitz B, Welliver RC, De Castro G, Krystofik DA, Ogra PL. 1988. The release of leukotrienes in the respiratory tract during infection with respiratory syncytial virus: role in obstructive airway disease. Pediatr Res 24:504-507. https://doi.org/10.1203/00006450-198810000-00018.
37. Bermejo-Martin JF, Garcia-Arevalol MC, De Lejarazu RO, Ardura J, Eiros JM, Alonso A, Matias V, Pino M, Bernardo D, Arranz E, Blanco-Quiros A. 2007. Predominance of Th2 cytokines, CXC chemokines and innate immunity mediators at the mucosal level during severe respiratory syncytial virus infection in children. Eur Cytokine Netw 18:162-167.
38. Chung HL, Kim SG. 2002. RANTES may be predictive of later recurrent wheezing after respiratory syncytial virus bronchiolitis in infants. Ann Allergy Asthma Immunol 88:463-467. https://doi.org/10.1016/S1081-1206(10)62383-6.
39. Okamoto N, Ikeda M, Okuda M, Sakamoto T, Takasugi M, Takahashi N, Araki T, Morishima T, Yasui K. 2011. Increased eosinophilic cationic protein in nasal fluid in hospitalized wheezy infants with RSV infection. Allergol Int 60:467-472. https://doi.org/10.2332/allergolint.10-OA-0263.
40. Smyth RL, Fletcher JN, Thomas HM, Hart CA. 1997. Immunological responses to respiratory syncytial virus infection in infancy. Arch Dis Child 76:210-214. https://doi.org/10.1136/adc.76.3.210.
41. Bermejo-Martin JF, Garcia-Arevalo MC, Alonso A, De Lejarazu RO, Pino M, Resino S, Tenorio A, Bernardo D, Leon AJ, Garrote JA, Ardura J, Dominguez-Gil M, Eiros JM, Blanco-Quiros A, Munoz-Fernandez MA, Kelvin DJ, Arranz E. 2007. Persistence of proinflammatory response after severe respiratory syncytial virus disease in children. J Allergy Clin Immunol 119:1547-1550. https://doi.org/10.1016/j.jaci.2007.03.014.
42. Roe MFE, Bloxham DM, White DK, Ross-Russell RI, Tasker RTC, O'Donnell DR. 2004. Lymphocyte apoptosis in acute respiratory syncytial virus bronchiolitis. Clin Exp Immunol 137:139-145. https://doi.org/10.1111/j.1365-2249.2004.02512.x.
43. Roman M, Calhoun WJ, Hinton KL, Avendano LF, Simon V, Escobar AM, Gaggero A, Diaz PV. 1997. Respiratory syncytial virus infection in infants is associated with predominant Th-2-like response. Am J Respi Crit Care Med 156:190-195. https://doi.org/10.1164/ajrccm.156.1.9611050.
44. Ribeiro LZG, Tripp RA, Rossi LMG, Palma PVB, Yokosawa J, Mantese OC, Oliveira TFM, Nepomuceno LL, Queiroz DAO. 2008. Serum mannosebinding lectin levels are linked with respiratory syncytial virus (RSV) disease. J Clin Immunol 28:166-173. https://doi.org/10.1007/s10875-007-9141-8.
45. Ayukawa H, Matsubara T, Kaneko M, Hasegawa M, Ichiyama T, Furukawa S. 2004. Expression of CTLA-4 (CD152) in peripheral blood T cells of children with influenza virus infection including encephalopathy in comparison with respiratory syncytial virus infection. Clin Exp Immunol 137:151-155. https://doi.org/10.1111/j.1365-2249.2004.02502.x.
46. Koga M, Matsuoka T, Matsubara T, Katayama K, Furukawa S. 2000. Different expression of ICAM-1 and LFA-1 alpha by peripheral leukocytes during respiratory syncytial virus and influenza virus infection in young children. Scand J Infect Dis 32:7-11. https://doi.org/10.1080/00365540050164146.
47. Aberle JH, Aberle SW, Dworzak MN, Mandl CW, Rebhandl W, Vollnhofer G, Kundi M, Popow-Kraupp T. 1999. Reduced interferon-gamma expression in peripheral blood mononuclear cells of infants with severe respiratory syncytial virus disease. Am J Respir Crit Care Med 160: 1263-1268. https://doi.org/10.1164/ajrccm.160.4.9812025.
48. Pinto RA, Arredondo SM, Bono MR, Gaggero AA, Diaz PV. 2006. T helper 1/T helper 2 cytokine imbalance in respiratory syncytial virus infection is associated with increased endogenous plasma cortisol. Pediatrics 117:e878-e886. https://doi.org/10.1542/peds.2005-2119.
49. de Waal L, Koopman LP, van Benten IJ, Brandenburg AH, Mulder PGH, de Swart RL, Fokkens WJ, Neijens HJ, Osterhaus A. 2003. Moderate local and systemic respiratory syncytial virus-specific T-cell responses upon mild or subclinical RSV infection. J Med Virol 70:309-318. https://doi.org/10.1002/jmv.10396.
50. Raiden S, Pandolfi J, Payaslian F, Anderson M, Rivarola N, Ferrero F, Urtasun M, Fainboim L, Geffner J, Arruvito L. 2014. Depletion of circulating regulatory T cells during severe respiratory syncytial virus infection in young children. Am J Respi Crit Care Med 189:865-868. https://doi.org/10.1164/rccm.201311-1977LE.
51. Li B, Wu FL, Feng XB, Sun DK, Cui QQ, Zhao ZX. 2012. Changes and the clinical significance of CD4(_) CD25(_) regulatory T cells and Th17 cells in peripheral blood of infants with respiratory syncytial virus bronchiolitis. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 28:426-428.
52. Bacharier LB, Coverstone A, Schweiger T, Gregory G, Yin-DeClue H, Sajol G, Giri T, Sierra O, Atkinson J, Wilson B, Zheng J, Schechtman K, Castro M. 2013. Regulatory T cells in acute severe RSV bronchiolitis, abstr 187. Abstr Am J Respir Crit Care Med Conf.
53. Isaacs D, Bangham CR, McMichael AJ. 1987. Cell-mediated cytotoxic response to respiratory syncytial virus in infants with bronchiolitis. Lancet ii:769-771.
54. Jozwik A, Habibi MS, Paras A, Zhu J, Guvenel A, Dhariwal J, Almond M, Wong EHC, Sykes A, Maybeno M, Del Rosario J, Trujillo-Torralbo MB, Mallia P, Sidney J, Peters B, Kon OM, Sette A, Johnston SL, Openshaw PJ, Chiu C. 2015. RSV-specific airway resident memory CD8_ T cells and differential disease severity after experimental human infection. Nat Commun 6:10224. https://doi.org/10.1038/ncomms10224.
55. Yao S, Jiang L, Moser EK, Jewett LB, Wright J, Du J, Zhou B, Davis SD, Krupp NL, Braciale TJ, Sun J. 2015. Control of pathogenic effector T-cell activities in situ by PD-L1 expression on respiratory inflammatory dendritic cells during respiratory syncytial virus infection. Mucosal Immunol 8:746-759. https://doi.org/10.1038/mi.2014.106.
56. de Souza APD, de Freitas D, Fernandes KEA, da Cunha MD, Fernandes JLA, Gassen RB, Fazolo T, Pinto LA, Scotta M, Mattiello R, Pitrez PM, Bonorino C, Stein RT. 2016. Respiratory syncytial virus induces phosphorylation of mTOR at ser2448 in CD8 T cells from nasal washes of infected infants. Clin Exp Immunol 183:248-257. https://doi.org/10.1111/cei.12720.
57. Tasker RC, Roe MFE, Bloxham DM, White DK, Ross-Russell RI, O'Donnell DR. 2004. The neuroendocrine stress response and severity of acute respiratory syncytial virus bronchiolitis in infancy. Intensive Care Med 30:2257-2262. https://doi.org/10.1007/s00134-004-2470-7.
58. Cherukuri A, Patton K, Gasser RA, Zuo FR, Woo J, Esser MT, Tang RS. 2013. Adults 65 years old and older have reduced numbers of functional memory T cells to respiratory syncytial virus fusion protein. Clin Vaccine Immunol 20:239-247. https://doi.org/10.1128/CVI.00580-12.
59. de Bree GJ, Heidema J, van Leeuwen EMM, van Bleek GM, Jonkers RE, Jansen HM, van Lier RAW, Out TA. 2005. Respiratory syncytial virusspecific CD8(+) memory T cell responses in elderly persons. J Infect Dis 191:1710-1718. https://doi.org/10.1086/429695.
60. Duncan MD, Wilkes DS. 2005. Transplant-related immunosuppression: a review of immunosuppression and pulmonary infections. Proc Am Thorac Soc 2:449-455. https://doi.org/10.1513/pats.200507-073JS.
61. Ljungman P, Ward KN, Crooks BN, Parker A, Martino R, Shaw PJ, Brinch L, Brune M, De La Camara R, Dekker A, Pauksen K, Russell N, Schwarer AP, Cordonnier C. 2001. Respiratory virus infections after stem cell transplantation: a prospective study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 28:479-484. https://doi.org/10.1038/sj.bmt.1703139.
62. McNamara PS, Ritson P, Selby A, Hart CA, Smyth RL. 2003. Bronchoalveolar lavage cellularity in infants with severe respiratory syncytial virus bronchiolitis. Arch Dis Child 88:922-926. https://doi.org/10.1136/adc.88.10.922.
63. Reed JL, Welliver TP, Sims GP, McKinney L, Velozo L, Avendano L, Hintz K, Luma J, Coyle AJ, Welliver RC. 2009. Innate immune signals modulate antiviral and polyreactive antibody responses during severe respiratory syncytial virus infection. J Infect Dis 199:1128-1138. https://doi.org/10.1086/597386.
64. Raes M, Peeters V, Alliet P, Gillis P, Kortleven J, Magerman K, Rummens JL. 1997. Peripheral blood T and B lymphocyte subpopulations in infants with acute respiratory syncytial virus brochiolitis. Pediatr Allergy Immunol 8:97-102. https://doi.org/10.1111/j.1399-3038.1997.tb00151.x.
65. Shinoff JJ, O'Brien KL, Thumar B, Shaw JB, Reid R, Hua W, Santosham M, Karron RA. 2008. Young infants can develop protective levels of neutralizing antibody after infection with respiratory syncytial virus. J Infect Dis 198:1007-1015. https://doi.org/10.1086/591460.
66. Strannegard O, Cello J, Bjarnason R, Sigurbergsson F, Sigurs N. 1997. Association between pronounced IgA response in RSV bronchiolitis and development of allergic sensitization. Pediatr Allergy Immunol 8:1-6. https://doi.org/10.1111/j.1399-3038.1997.tb00134.x.
67. McNamara PS, Fonceca AM, Howarth D, Correia JB, Slupsky JR, Trinick RE, Al Turaiki W, Smyth RL, Flanagan BF. 2013. Respiratory syncytial virus infection of airway epithelial cells, in vivo and in vitro, supports pulmonary antibody responses by inducing expression of the B cell differentiation factor BAFF. Thorax 68:76-81. https://doi.org/10.1136/thoraxjnl-2012-202288.
68. Fonceca A, McNamara P, Howarth D, Trinick R, Alturaiki W, Smyth R, Flanagan B. 2011. Human respiratory syncytial virus infection in vivo and in vitro induces airway epithelial cell expression of the B cell differentiation factor BAFF. Immunology 135:94.
69. Jensen IP, Thisted E, Glikmann G, Obel N, Kofoed PE, Sambo M, Valerius NH, Mordhorst CH. 1997. Secretory IgM and IgA antibodies to respiratory syncytial virus in nasopharyngeal aspirates: a diagnostic supplement to antigen detection. Clin Diagn Virol 8:219-226. https://doi.org/10.1016/S0928-0197(97)10002-2.
70. Lee FEH, Falsey AR, Halliley JL, Sanz I, Walsh EE. 2010. Circulating antibodysecreting cells during acute respiratory syncytial virus infection in adults. J Infect Dis 202:1659-1666. https://doi.org/10.1086/657158.
71. Agius G, Dindinaud G, Biggar RJ, Peyre R, Vaillant V, Ranger S, Poupet JY, Cisse MF, Castets M. 1990. An epidemic of respiratory syncytial virus in elderly people: clinical and serological findings. J Med Virol 30: 117-127. https://doi.org/10.1002/jmv.1890300208.
72. Forster J, Maier O, Lobbert J, Kaufmehl K, Streckert HJ, Werchau H. 1996. Prevalence of antibodies against HEp-2 cell antigen in infants and children hospitalized with respiratory syncytial virus infection. Infection 24:407-411. https://doi.org/10.1007/BF01713039.
73. Bagga B, Cehelsky JE, Vaishnaw A, Wilkinson T, Meyers R, Harrison LM, Roddam PL, Walsh EE, DeVincenzo JP. 2015. Effect of preexisting serum and mucosal antibody on experimental respiratory syncytial virus (RSV) challenge and infection of adults. J Infect Dis 212:1719-1725. https://doi.org/10.1093/infdis/jiv281.
74. Habibi MS, Jozwik A, Makris S, Dunning J, Paras A, DeVincenzo JP, de Haan CAM, Wrammert J, Openshaw PJM, Chiu C, Mechanisms of Severe Acute Influenza Consortium Investigators. 2015. Impaired antibodymediated protection and defective IgA B-cell memory in experimental infection of adults with respiratory syncytial virus. Am J Respir Crit Care Med 191:1040-1049. https://doi.org/10.1164/rccm.201412-2256OC.
75. Bagga B, Cehelsky J, Vaishnaw A, Wilkinson T, Meyers R, Harrison L, Roddam P, Walsh EE, DeVincenzo JP. 2011. Effect of serum and mucosal antibody on experimental RSV infections of adults. J Invest Med 59: 487-488.
76. Hall CB, Walsh EE, Long CE, Schnabel KC. 1991. Immunity to and frequency of reinfection with respiratory syncytial virus. J Infect Dis 163:693-698. https://doi.org/10.1093/infdis/163.4.693.
77. Lee FEH, Walsh EE, Falsey AR, Betts RE, Treanor JJ. 2004. Experimental infection of humans with A2 respiratory syncytial virus. Antiviral Res 63:191-196. https://doi.org/10.1016/j.antiviral.2004.04.005.
78. Walsh EE, Falsey AR. 2004. Humoral and mucosal immunity in protection from natural respiratory syncytial virus infection in adults. J Infect Dis 190:373-378. https://doi.org/10.1086/421524.
79. Falsey AR, Walsh EE. 1998. Relationship of serum antibody to risk of respiratory syncytial virus infection in elderly adults. J Infect Dis 177: 463-466. https://doi.org/10.1086/517376.
80. Medrano Gonzalez L, Jozwik AA, Habibi MS, Openshaw PJM, Chiu C. 2014. Quality of antigen-specific B-cell responses as a correlate of protection against RSV. Immunology 143:75.
81. Tsutsumi H, Matsuda K, Yamazaki H, Ogra PL, Chiba S. 1995. Different kinetics of antibody responses between IgA and IgG classes in nasopharyngeal secretion in infants and children during primary respiratory syncytial virus infection. Acta Paediatr Japonica 37:464-468. https://doi.org/10.1111/j.1442-200X.1995.tb03356.x.
82. Freitas GRO, Silva DAO, Yokosawa J, Paula NT, Costa LF, Carneiro BM, Ribeiro LZG, Oliveira TFM, Mineo JR, Queiroz DAO. 2011. Antibody response and avidity of respiratory syncytial virus-specific total IgG, IgG1, and IgG3 in young children. J Med Virol 83:1826-1833. https://doi.org/10.1002/jmv.22134.
83. Murphy BR, Graham BS, Prince GA, Walsh EE, Chanock RM, Karzon DT, Wright PF. 1986. Serum and nasal-wash immunoglobulin G and A antibody response of infants and children to respiratory syncytial virus F and G glycoproteins following primary infection. J Clin Microbiol 23:1009-1014.
84. Yamazaki H, Tsutsumi H, Matsuda K, Nagai K, Ogra PL, Chiba S. 1994. Effect of maternal antibody on IgA antibody response in nasopharyngeal secretion in infants and children during primary respiratory syncytial virus infection. J Gen Virol 75:2115-2119. https://doi.org/10.1099/0022-1317-75-8-2115.
85. Falsey AR, Singh HK, Walsh EE. 2006. Serum antibody decay in adults following natural respiratory syncytial virus infection. J Med Virol 78: 1493-1497. https://doi.org/10.1002/jmv.20724.
86. Sande CJ, Mutunga MN, Medley GF, Cane PA, Nokes DJ. 2013. Groupand genotype-specific neutralizing antibody responses against respiratory syncytial virus in infants and young children with severe pneumonia. J Infect Dis 207:489-492. https://doi.org/10.1093/infdis/jis700.
87. Yamazaki H, Tsutsumi H, Matsuda K, Nagai K, Ogra PL, Chiba S. 1994. Respiratory syncytial virus group-specific antibody response in nasopharyngeal secretions from infants and children after primary infection. Clin Diagn Lab Immunol 1:469-472.
88. McGill A, Greensill J, Marsh R, Craft AW, Toms GL. 2004. Detection of human respiratory syncytial virus genotype specific antibody responses in infants. J Med Virol 74:492-498. https://doi.org/10.1002/jmv.20203.
89. Kaul TN, Welliver RC, Ogra PL. 1982. Appearance of complement components and immunoglobulins on nasopharyngeal epithelial cells following naturally acquired infection with respiratory syncytial virus. J Med Virol 9:149-158. https://doi.org/10.1002/jmv.1890090210.
90. Kaul TN, Welliver RC, Faden HS, Ogra PL. 1984. The development of respiratory syncytial virus-specific immune complexes in nasopharyngeal secretions following natural infection. J Clin Lab Immunol 15: 187-190.
91. Kaul TN, Welliver RC, Ogra PL. 1982. Development of antibodydependent cell-mediated cytotoxicity in the respiratory tract after natural infection with respiratory syncytial virus. Infect Immun 37:492-498.
92. Russi JC, Delfraro A, Borthagaray MD, Velazquez B, Garcia-Barreno B, Hortal M. 1993. Evaluation of immunoglobulin E-specific antibodies and viral antigens in nasopharyngeal secretions of children with respiratory syncytial virus infections. J Clin Microbiol 31:819-823.
93. Rabatic S, Gagro A, Lokar-Kolbas R, Krsulovic-Hresic V, Vrtar Z, Popow-Kraupp T, Drazenovic V, Mlinaric-Galinovic G. 1997. Increase in CD23_ B cells in infants with bronchiolitis is accompanied by appearance of IgE and IgG4 antibodies specific for respiratory syncytial virus. J Infect Dis 175:32-37. https://doi.org/10.1093/infdis/175.1.32.
94. Welliver RC, Wong DT, Sun M, Middleton E, Jr, Vaughan RS, Ogra PL. 1981. The development of respiratory syncytial virus-specific IgE and the release of histamine in nasopharyngeal secretions after infection. N Engl J Med 305:841-846. https://doi.org/10.1056/NEJM198110083051501.
95. Chung HL, Jang YY. 2016. High serum IgE level in the children with acute respiratory syncytial virus infection is associated with severe disease. J Allergy Clin Immunol 137:AB110.
96. Welliver RC, Duffy L. 1993. The relationship of RSV-specific immunoglobulin E antibody responses in infancy, recurrent wheezing, and pulmonary function at age 7-8 years. Pediatr Pulmonol 15:19-27. https://doi.org/10.1002/ppul.1950150104.
97. Ye Q, Shao WX, Shang SQ, Pan YX, Shen HQ, Chen XJ. 2015. Epidemiological characteristics and immune status of children with respiratory syncytial virus. J Med Virol 87:323-329. https://doi.org/10.1002/jmv.24047.
98. Hattori S, Shimojo N, Mashimo T, Inoue Y, Ono Y, Kohno Y, Okamoto Y, Hata A, Suzuki Y. 2011. Relationship between RANTES polymorphisms and respiratory syncytial virus bronchiolitis in a Japanese infant population. Jpn J Infect Dis 64:242-245.
99. Fernandez JA, Roine I, Vazquez A, Caneo M. 2005. Soluble interleukin-2 receptor (sCD25) and interleukin-10 plasma concentrations are associated with severity of primary respiratory syncytial virus (RSV) infection. Eur Cytokine Netw 16:81-90.
100. Fernandez JA, Tapia L, Palomino MA, Larranaga C, Pena M, Jaramillo H. 2005. Plasma interferon-gamma, interleukin-10 and soluble markers of immune activation in infants with primary adenovirus (ADV) and respiratory syncytial virus (RSV) infection. Eur Cytokine Netw 16:35-40.
101. Chung HL, Park HJ, Kim SY, Kim SG. 2007. Age-related difference in immune responses to respiratory syncytial virus infection in young children. Pediatr Allergy Immunol 18:94-99. https://doi.org/10.1111/j.1399-3038.2006.00501.x.
102. Bont L, Heijnen CJ, Kavelaars A, van Aalderen WMC, Brus F, Draaisma JTM, Geelen SM, van Vught HJ, Kimpen JLL. 1999. Peripheral blood cytokine responses and disease severity in respiratory syncytial virus bronchiolitis. Eur Respir J 14:144-149. https://doi.org/10.1034/j.1399-3003.1999.14a24.x.
103. Garofalo RP, Patti J, Hintz KA, Hill V, Ogra PL, Welliver RC. 2001. Macrophage inflammatory protein-1 alpha (not T helper type 2 cytokines) is associated with severe forms of respiratory syncytial virus bronchiolitis. J Infect Dis 184:393-399. https://doi.org/10.1086/322788.
104. Kim CK, Callaway Z, Koh YY, Kim SH, Fujisawa T. 2012. Airway IFNgamma production during RSV bronchiolitis is associated with eosinophilic inflammation. Lung 190:183-188. https://doi.org/10.1007/s00408-011-9349-5.
105. Choi J, Callaway Z, Kim HB, Fujisawa T, Kim CK. 2010. The role of TNF-alpha in eosinophilic inflammation associated with RSV bronchiolitis. Pediatr Allergy Immunol 21:474-479. https://doi.org/10.1111/j.1399-3038.2009.00908.x.
106. Semple MG, Dankert HM, Ebrahimi B, Correia JB, Booth JA, Stewart JP, Smyth RL, Hart CA. 2007. Severe respiratory syncytial virus bronchiolitis in infants is associated with reduced airway interferon gamma and substance P. PLoS One 2:e1038. https://doi.org/10.1371/journal.pone.0001038.
107. Garcia C, Soriano-Fallas A, Lozano J, Leos N, Gomez AM, Ramilo O, Mejias A. 2012. Decreased innate immune cytokine responses correlate with disease severity in children with respiratory syncytial virus and human rhinovirus bronchiolitis. Pediatr Infect Dis J 31:86-89. https://doi.org/10.1097/INF.0b013e31822dc8c1.
108. Bennett BL, Garofalo RP, Cron SG, Hosakote YM, Atmar RL, Macias CG, Piedra PA. 2007. Immunopathogenesis of respiratory syncytial virus bronchiolitis. J Infect Dis 195:1532-1540. https://doi.org/10.1086/515575.
109. Kristjansson S, Bjarnarson SP, Wennergren G, Palsdottir AH, Arnadottir T, Haraldsson A, Jonsdottir I. 2005. Respiratory syncytial virus and other respiratory viruses during the first 3 months of life promote a local TH2-like response. J Allergy Clin Immunol 116:805-811. https://doi.org/10.1016/j.jaci.2005.07.012.
110. Bont L, Heijnen CJ, Kavelaars A, van Aalderen WMC, Brus F, Draaisma JMT, Pekelharing-Berghuis M, van Diemen-Steenvoorde R, Kimpen JLL. 2001. Local interferon-gamma levels during respiratory syncytial virus lower respiratory tract infection are associated with disease severity. J Infect Dis 184:355-358. https://doi.org/10.1086/322035.
111. Diaz PV, Gaggero AA, Pinto RA, Mamani R, Uasapud PA, Bono MR. 2013. Levels of inflammatory cytokines and plasma cortisol in respiratory syncytial virus bronchiolitis. Rev Med Chile 141:574-581. https://doi.org/10.4067/S0034-98872013000500004.
112. Giugno KM, Machado DC, Amantea SL, Menna Barreto SS. 2004. Concentrations of interleukin-2 in the nasopharyngeal secretion of children with acute respiratory syncytial virus bronchiolitis. J Pediatria 80: 315-320. (In Portuguese.) https://doi.org/10.2223/1206,10.2223/JPED.1206.
113. McNamara PS, Flanagan BF, Selby AM, Hart CA, Smyth RL. 2004. Proand anti-inflammatory responses in respiratory syncytial virus bronchiolitis. Eur Respir J 23:106-112. https://doi.org/10.1183/09031936.03.00048103.
114. van Benten IJ, van Drunen CM, Koevoet JLM, Koopman LP, Hop WCJ, Osterhaus A, Neijens HJ, Fokkens WJ. 2005. Reduced nasal IL-10 and enhanced TNF alpha responses during rhinovirus and RSV-induced upper respiratory tract infection in atopic and non-atopic infants. J Med Virol 75:348-357. https://doi.org/10.1002/jmv.20277.
115. Matsuda K, Tsutsumi H, Okamoto Y, Chiba C. 1995. Development of interleukin 6 and tumor necrosis factor alpha activity in nasopharyngeal secretions of infants and children during infection with respiratory syncytial virus. Clin Diagn Lab Immunol 2:322-324.
116. Hornsleth A, Klug B, Nir M, Johansen J, Hansen KS, Christensen LS, Larsen LB. 1998. Severity of respiratory syncytial virus disease related to type and genotype of virus and to cytokine values in nasopharyngeal secretions. Pediatr Infect Dis J 17:1114-1121. https://doi.org/10.1097/00006454-199812000-00003.
117. van Benten IJ, van Drunen CM, Koopman LP, KleinJan A, van Middelkoop BC, de Waal L, Osterhaus A, Neijens HJ, Fokkens WJ. 2003. RSVinduced bronchiolitis but not upper respiratory tract infection is accompanied by an increased nasal IL-18 response. J Med Virol 71: 290-297. https://doi.org/10.1002/jmv.10482.
118. Faber TE, Groen H, Welfing M, Jansen KJG, Bont LJ. 2012. Specific increase in local IL-17 production during recovery from primary RSV bronchiolitis. J Med Virol 84:1084-1088. https://doi.org/10.1002/jmv.23291.
119. Tabarani CM, Bonville CA, Suryadevara M, Branigan P, Wang D, Huang D, Rosenberg HF, Domachowske JB. 2013. Novel inflammatory markers, clinical risk factors and virus type associated with severe respiratory syncytial virus infection. Pediatr Infect Dis J 32:e437-442. https://doi.org/10.1097/INF.0b013e3182a14407.
120. Garofalo RP, Hintz KH, Hill V, Ogra PL, Welliver RC. 2004. Production of interferon gamma in respiratory syncytial virus infection of humans is not associated with interleukins 12 and 18. J Med Virol 73:289-294. https://doi.org/10.1002/jmv.20089.
121. Mella C, Suarez-Arrabal MC, Lopez S, Stephens J, Fernandez S, Hall MW, Ramilo O, Mejias A. 2013. Innate immune dysfunction is associated with enhanced disease severity in infants with severe respiratory syncytial virus bronchiolitis. J Infect Dis 207:564-573. https://doi.org/10.1093/infdis/jis721.
122. Diaz PV, Pinto RA, Mamani R, Uasapud PA, Bono MR, Gaggero AA, Guerrero J, Goecke A. 2012. Increased expression of the glucocorticoid receptor beta in infants with RSV bronchiolitis. Pediatrics 130: E804-E811. https://doi.org/10.1542/peds.2012-0160.
123. Hassan MA, Eldin AM, Ahmed MM. 2008. T-helper2/T-helper1 imbalance in respiratory syncytial virus bronchiolitis in relation to disease severity and outcome. Egyptian J Immunol 15:153-160.
124. Vieira RA, Diniz EMA, Mejr C. 2010. Concentrations of inflammatory mediators in Brazilian newborn with respiratory syncytial virus lower respiratory tract infection. J Maternal-Fetal Neonatal Med 23:635-636.
125. Vieira RA, Diniz EM, Ceccon ME. 2010. Correlation between inflammatory mediators in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection caused by respiratory syncytial virus and disease severity. J Bras Pneumol 36:59-66. https://doi.org/10.1590/S1806-37132010000100011.
126. Sung RYT, Hui SHL, Wong CK, Lam CWK, Yin J. 2001. A comparison of cytokine responses in respiratory syncytial virus and influenza A infections in infants. Eur J Pediatr 160:117-122. https://doi.org/10.1007/s004310000676.
127. Midulla F, Tromba V, Lo Russo L, Mileto F, Sabatino G, Sgarrella M, Panuska JR, Manganozzi L, Korn D, Moret C. 2006. Cytokines in the nasal washes of children with respiratory syncytial virus bronchiolitis. Int J Immunopathol Pharmacol 19:231-235.
128. Chung HL, Kim WT, Kim JK, Choi EJ, Lee JH, Lee GH, Kim SG. 2005. Relationship between atopic status and nasal interleukin 10 and 11 levels in infants with respiratory syncytial virus bronchiolitis. Ann Allergy Asthma Immunol 94:267-272. https://doi.org/10.1016/S1081-1206(10)61307-5.
129. Murai H, Terada A, Mizuno M, Asai M, Hirabayashi Y, Shimizu S, Morishita T, Kakita H, Hussein MH, Ito T, Kato I, Asai K, Togari H. 2007. IL-10 and RANTES are elevated in nasopharyngeal secretions of children with respiratory syncytial virus infection. Allergol Int 56:157-163. https://doi.org/10.2332/allergolint.O-06-454.
130. Saravia J, You D, Shrestha B, Jaligama S, Siefker D, Lee GI, Harding JN, Jones TL, Rovnaghi C, Bagga B, DeVincenzo JP, Cormier SA. 2015. Respiratory syncytial virus disease is mediated by age-variable IL-33. PLoS Pathog 11:e1005217. https://doi.org/10.1371/journal.ppat.1005217.
131. McNamara PS, Flanagan BF, Baldwin LM, Newland P, Hart CA, Smyth RL. 2004. Interleukin 9 production in the lungs of infants with severe respiratory syncytial virus bronchlolitis. Lancet 363:1031-1037. https://doi.org/10.1016/S0140-6736(04)15838-8.
132. Sheeran P, Jafri H, Carubelli C, Saavedra J, Johnson C, Krisher K, Sanchez PJ, Ramilo O. 1999. Elevated cytokine concentrations in the nasopharyngeal and tracheal secretions of children with respiratory syncytial virus disease. Pediatr Infect Dis J 18:115-122. https://doi.org/10.1097/00006454-199902000-00007.
133. Bertrand P, Lay MK, Piedimonte G, Brockmann PE, Palavecino CE, Hernandez J, Leon MA, Kalergis AM, Bueno SM. 2015. Elevated IL-3 and IL-12p40 levels in the lower airway of infants with RSV-induced bronchiolitis correlate with recurrent wheezing. Cytokine 76:417-423. https://doi.org/10.1016/j.cyto.2015.07.017.
134. Hornsleth A, Loland L, Larsen LB. 2001. Cytokines and chemokines in respiratory secretion and severity of disease in infants with respiratory syncytial virus (RSV) infection. J Clin Virol 21:163-170. https://doi.org/10.1016/S1386-6532(01)00159-7.
135. Brandenburg AH, Kleinjan A, van't Land B, Moll HA, Timmerman HH, de Swart RL, Neijens HJ, Fokkens W, Osterhaus A. 2000. Type 1-like immune response is found in children with respiratory syncytial virus infection regardless of clinical severity. J Med Virol 62:267-277.
136. Diaz PV, Valdivia G, Gaggero AA, Bono MR, Zepeda G, Rivas M, Uasapud P, Pinto RA, Boza ML, Guerrero J. 2015. Pro-inflammatory cytokines in nasopharyngeal aspirate from hospitalized children with respiratory syncytial virus infection with or without rhinovirus bronchiolitis, and use of the cytokines as predictors of illness severity. Medicine 94:e1512. https://doi.org/10.1097/MD.0000000000001512.
137. Walsh EE, Peterson DR, Kalkanoglu AE, Lee FE, Falsey AR. 2013. Viral shedding and immune responses to respiratory syncytial virus infection in older adults. J Infect Dis 207:1424-1432. https://doi.org/10.1093/infdis/jit038.
138. DeVincenzo JP, Wilkinson T, Vaishnaw A, Cehelsky J, Meyers R, Nochur S, Harrison L, Meeking P, Mann A, Moane E, Oxford J, Pareek R, Moore R, Walsh E, Studholme R, Dorsett P, Alvarez R, Lambkin-Williams R. 2010. Viral load drives disease in humans experimentally infected with respiratory syncytial virus. Am J Respir Crit Care Med 182:1305-1314. https://doi.org/10.1164/rccm.201002-0221OC.
139. Caballero MT, Serra ME, Acosta PL, Marzec J, Gibbons L, Salim M, Rodriguez A, Reynaldi A, Garcia A, Bado D, Buchholz UJ, Hijano DR, Coviello S, Newcomb D, Bellabarba M, Ferolla FM, Libster R, Berenstein A, Siniawaski S, Blumetti V, Echavarria M, Pinto L, Lawrence A, Ossorio MF, Grosman A, Mateu CG, Bayle C, Dericco A, Pellegrini M, Igarza I, Repetto HA, Grimaldi LA, Gudapati P, Polack NR, Althabe F, Shi M, Ferrero F, Berge E, Stein RT, Peebles RS, Boothby M, Kleeberger SR, Polack FP. 2015. TLR4 genotype and environmental LPS mediate RSV bronchiolitis through Th2 polarization. J Clin Invest 125:571-582. https://doi.org/10.1172/JCI75183.
140. Roe MFE, Bloxham DM, Cowburn AS, O'Donnell DR. 2011. Changes in helper lymphocyte chemokine receptor expression and elevation of IP-10 during acute respiratory syncytial virus infection in infants. Pediatr Allergy Immunol 22:229-234. https://doi.org/10.1111/j.1399-3038.2010.01032.x.
141. Legg JP, Hussain IR, Warner JA, Johnston SL, Warner JO. 2003. Type 1 and type 2 cytokine imbalance in acute respiratory syncytial virus bronchiolitis. Am J Respir Crit Care Med 168:633-639. https://doi.org/10.1164/rccm.200210-1148OC.
142. Chen ZM, Mao JH, Du LZ, Tang YM. 2002. Association of cytokine responses with disease severity in infants with respiratory syncytial virus infection. Acta Paediatr 91:914-922. https://doi.org/10.1111/j.1651-2227.2002.tb02877.x.
143. Pancham K, Perez GF, Husen S, Jain A, Kurdi B, Rodriguez-Martinez CE, Preciado D, Rose MC, Nino G. 2015. Premature infants have impaired airway antiviral IFN gamma responses to human metapneumovirus compared to respiratory syncytial virus. Pediatr Res 78:389-394. https://doi.org/10.1038/pr.2015.113.
144. Mobbs KJ, Smyth RL, O'Hea U, Ashby D, Ritson P, Hart CA. 2002. Cytokines in severe respiratory syncytial virus bronchiolitis. Pediatr Pulmonol 33:449-452. https://doi.org/10.1002/ppul.10101.
145. Looney RJ, Falsey AR, Walsh E, Campbell D. 2002. Effect of aging on cytokine production in response to respiratory syncytial virus infection. J Infect Dis 185:682-685. https://doi.org/10.1086/339008.
146. Noah TL, Ivins SS, Murphy P, Kazachkova I, Moats-Staats B, Henderson FW. 2002. Chemokines and inflammation in the nasal passages of infants with respiratory syncytial virus bronchiolitis. Clin Immunol 104: 86-95. https://doi.org/10.1006/clim.2002.5248.
147. Smyth RL, Mobbs KJ, O'Hea U, Ashby D, Hart CA. 2002. Respiratory syncytial virus bronchiolitis: disease severity, interleukin-8, and virus genotype. Pediatr Pulmonol 33:339-346. https://doi.org/10.1002/ppul.10080.
148. Biswas S, Friedland JS, Remick DG, Davies EG, Sharland M. 1995. Elevated plasma interleukin 8 in respiratory syncytial virus bronchiolitis. Pediatr Infect Dis J 14:919. https://doi.org/10.1097/00006454-199510000-00027.
149. Noah TL, Becker S. 2000. Chemokines in nasal secretions of normal adults experimentally infected with respiratory syncytial virus. Clin Immunol 97:43-49. https://doi.org/10.1006/clim.2000.4914.
150. Adams O, Weis J, Jasinska K, Vogel M, Tenenbaum T. 2015. Comparison of human metapneumovirus, respiratory syncytial virus and rhinovirus respiratory tract infections in young children admitted to hospital. J Med Virol 87:275-280. https://doi.org/10.1002/jmv.24025.
151. Assefa D, Amin N, Dozor AJ, Parton LA. 2011. Attenuated interleukin-8/leukocyte immunoresponse in preterm infants compared with term infants hospitalized with respiratory syncytial virus bronchiolitis: a pilot study. Hum Immunol 72:708-711. https://doi.org/10.1016/j.humimm.2011.05.016.
152. Stoppelenburg AJ, Salimi V, Hennus M, Plantinga M, in 't Veld RH, Walk J, Meerding J, Coenjaerts F, Bont L, Boes M. 2013. Local IL-17A potentiates early neutrophil recruitment to the respiratory tract during severe RSV infection. PLoS One 8:e78461. https://doi.org/10.1371/journal.pone.0078461.
153. McNamara PS, Flanagan BF, Hart CA, Smyth RL. 2005. Production of chemokines in the lungs of infants with severe respiratory syncytial virus bronchiolitis. J Infect Dis 191:1225-1232. https://doi.org/10.1086/428855.
154. Becker S, Reed W, Henderson FW, Noah TL. 1997. RSV infection of human airway epithelial cells causes production of the beta-chemokine RANTES. Am J Physiol 272:L512-L520.
155. Garofalo RP, Olszewska-Pazdrak B, Ogra PL, Welliver RC. 2001. Betachemokines in nasal secretions of infants with respiratory syncytial virus-induced respiratory infections. Pediatr Asthma Allergy Immunol 15:89-96. https://doi.org/10.1089/088318701753436880.
156. Garofalo RP, Hintz KH, Hill V, Patti J, Ogra PL, Welliver RC. 2005. A comparison of epidemiologic and immunologic features of bronchiolitis caused by influenza virus and respiratory syncytial virus. J Med Virol 75:282-289. https://doi.org/10.1002/jmv.20268.
157. Scagnolari C, Midulla F, Pierangeli A, Moretti C, Bonci E, Berardi R, De Angelis D, Selvaggi C, Di Marco P, Girardi E, Antonelli G. 2009. Gene expression of nucleic acid-sensing pattern recognition receptors in children hospitalized for respiratory syncytial virus-associated acute bronchiolitis. Clin Vaccine Immunol 16:816-823. https://doi.org/10.1128/CVI.00445-08.
158. Nakayama T, Sonoda S, Urano T, Sasaki K, Maehara N, Makino S. 1993. Detection of alpha-interferon in nasopharyngeal secretions and sera in children infected with respiratory syncytial virus. Pediatr Infect Dis J 12:925-929. https://doi.org/10.1097/00006454-199311000-00007.
159. Selvaggi C, Pierangeli A, Fabiani M, Spano L, Nicolai A, Papoff P, Moretti C, Midulla F, Antonelli G, Scagnolari C. 2014. Interferon lambda 1-3 expression in infants hospitalized for RSV or HRV associated bronchiolitis. J Infect 68:467-477. https://doi.org/10.1016/j.jinf.2013.12.010.
160. Nenna R, Ferrara M, Nicolai A, Pierangeli A, Scagnolari C, Papoff P, Antonelli G, Moretti C, Midulla F. 2015. Viral load in infants hospitalized for respiratory syncytial virus bronchiolitis correlates with recurrent wheezing at thirty-six-month follow-up. Pediatr Infect Dis J 34: 1131-1132. https://doi.org/10.1097/INF.0000000000000825.
161. Sun Y, Jain D, Koziol-White CJ, Genoyer E, Gilbert M, Tapia K, Panettieri RA, Hodinka RL, Lopez CB. 2015. Immunostimulatory defective viral genomes from respiratory syncytial virus promote a strong innate antiviral response during infection in mice and humans. PLoS Pathog 11:e1005122. https://doi.org/10.1371/journal.ppat.1005122.
162. Inchley CS, Sonerud T, Fjaerli HO, Nakstad B. 2015. Nasal mucosal microRNA expression in children with respiratory syncytial virus infection. BMC Infect Dis 15:150. https://doi.org/10.1186/s12879-015-0878-z.
163. Liu S, Gao L, Wang X, Xing Y. 2015. Respiratory syncytial virus infection inhibits TLR4 signaling via up-regulation of miR-26b. Cell Biol Int 39:1376-1383. https://doi.org/10.1002/cbin.10518.
164. Mejias A, Dimo B, Suarez NM, Garcia C, Suarez-Arrabal MC, Jartti T, Blankenship D, Jordan-Villegas A, Ardura MI, Xu ZH, Banchereau J, Chaussabel D, Ramilo O. 2013. Whole blood gene expression profiles to assess pathogenesis and disease severity in infants with respiratory syncytial virus infection. PLoS Med 10:e1001549. https://doi.org/10.1371/journal.pmed.1001549.
165. Bucasas KL, Mian AI, Demmler-Harrison GJ, Caviness AC, Piedra PA, Franco LM, Shaw CA, Zhai YJ, Wang XQ, Bray MS, Couch RB, Belmont JW. 2013. Global gene exprssion profiling in infants with acute respiratory syncytial virus broncholitis demonstrates systemic activation of interferon signaling networks. Pediatr Infect Dis J 32:E68-E76. https://doi.org/10.1097/INF.0b013e318278b4b3.
166. Fjaerli HO, Bukholm G, Krog A, Skjaeret C, Holden M, Nakstad B. 2006. Whole blood gene expression in infants with respiratory syncytial virus bronchiolitis. BMC Infect Dis 6:175. https://doi.org/10.1186/1471-2334-6-175.
167. van den Kieboom CH, Ahout IML, Zomer A, Brand KH, de Groot R, Ferwerda G, de Jonge MI. 2015. Nasopharyngeal gene expression, a novel approach to study the course of respiratory syncytial virus infection. Eur Respir J 45:718-725. https://doi.org/10.1183/09031936.00085614.
168. Seed PC. 2016. Do bacteria in the gut set the stage for who gets viral bronchiolitis and its severity? Pediatrics 138:e20161377. https://doi.org/10.1542/peds.2016-1377.
169. Prevaes SM, de Winter-de Groot KM, Janssens HM, de Steenhuijsen Piters WA, Tramper-Stranders GA, Wyllie AL, Hasrat R, Tiddens HA, van Westreenen M, van der Ent CK, Sanders EA, Bogaert D. 2016. Development of the nasopharyngeal microbiota in infants with cystic fibrosis. Am J Respir Crit Care Med 193:504-515. https://doi.org/10.1164/rccm.201509-1759OC.
170. de Steenhuijsen Piters WA, Heinonen S, Hasrat R, Bunsow E, Smith B, Suarez-Arrabal MC, Chaussabel D, Cohen DM, Sanders EA, Ramilo O, Bogaert D, Mejias A. 2016. Nasopharyngeal microbiota, host transcriptome, and disease severity in children with respiratory syncytial virus infection. Am J Respir Crit Care Med 194:1104-1115. https://doi.org/10.1164/rccm.201602-0220OC.
171. Zomer-Kooijker K, van der Ent CK, Ermers MJ, Uiterwaal CS, Rovers MM, Bont LJ. 2014. Increased risk of wheeze and decreased lung function after respiratory syncytial virus infection. PLoS One 9:e87162. https://doi.org/10.1371/journal.pone.0087162.
172. Blanken MO, Rovers MM, Molenaar JM, Winkler-Seinstra PL, Meijer A, Kimpen JL, Bont L. 2013. Respiratory syncytial virus and recurrent wheeze in healthy preterm infants. N Engl J Med 368:1791-1799. https://doi.org/10.1056/NEJMoa1211917.
173. Pino M, Kelvin DJ, Bermejo-Martin JF, Alonso A, Matias V, Tenorio A, Rico L, Eiros JM, Castrodeza J, Blanco-Quiros A, Ardura J, de Lejarazu RO. 2009. Nasopharyngeal aspirate cytokine levels 1 yr after severe respiratory syncytial virus infection. Pediatr Allergy Immunol 20: 791-795. https://doi.org/10.1111/j.1399-3038.2009.00868.x.
174. Kitcharoensakkul M, Bacharier LB, Yin-Declue H, Schweiger T, Goss CW, Boomer JS, Sajol G, Schectman K, Castro M. 2016. Increased nasal plasmacytoid dendritic cells are associated with recurrent wheezing following severe RSV bronchiolitis. J Allergy Clin Immunol 137:AB411. https://doi.org/10.1016/j.jaci.2015.12.1321.
175. Borchers AT, Chang C, Gershwin ME, Gershwin LJ. 2013. Respiratory syncytial virus-a comprehensive review. Clin Rev Allergy Immunol 45:331-379. https://doi.org/10.1007/s12016-013-8368-9.
176. Knudson CJ, Hartwig SM, Meyerholz DK, Varga SM. 2015. RSV vaccineenhanced disease is orchestrated by the combined actions of distinct CD4 T cell subsets. PLoS Pathog 11:e1004757. https://doi.org/10.1371/journal.ppat.1004757.
177. Currie SM, Findlay EG, McFarlane AJ, Fitch PM, Bottcher B, Colegrave N, Paras A, Jozwik A, Chiu C, Schwarze J, Davidson DJ. 2016. Cathelicidins have direct antiviral activity against respiratory syncytial virus in vitro and protective function in vivo in mice and humans. J Immunol 196: 2699-2710. https://doi.org/10.4049/jimmunol.1502478.
178. Kerr MH, Paton JY. 1999. Surfactant protein levels in severe respiratory syncytial virus infection. Am J Respir Crit Care Med 159:1115-1118. https://doi.org/10.1164/ajrccm.159.4.9709065.
179. Dargaville PA, South M, McDougall PN. 1996. Surfactant abnormalities in infants with severe viral bronchiolitis. Arch Dis Child 75:133-136. https://doi.org/10.1136/adc.75.2.133.
180. Skelton R, Holland P, Darowski M, Chetcuti PA, Morgan LW, Harwood JL. 1999. Abnormal surfactant composition and activity in severe bronchiolitis. Acta Paediatr 88:942-946. https://doi.org/10.1111/j.1651-2227.1999.tb00186.x.
181. Wang SZ, Doyle IR, Nicholas TE, Forsyth KD. 1999. Plasma surfactant protein-B is elevated in infants with respiratory syncytial virus-induced bronchiolitis. Pediatr Res 46:731-734. https://doi.org/10.1203/00006450-199912000-00023.
182. Kong MY, Clancy JP, Peng N, Li Y, Szul TJ, Xu X, Oster R, Sullender W, Ambalavanan N, Blalock JE, Gaggar A. 2014. Pulmonary matrix metalloproteinase-9 activity in mechanically ventilated children with respiratory syncytial virus. Eur Respir J 43:1086-1096. https://doi.org/10.1183/09031936.00105613.
183. Kong M, Peng N, Jackson P, Clancy J, Blalock E, Gaggar A. 2012. 174: dysregulated matrix metalloproteinase-9 activity and elevated prolineglycine-proline (pgp) levels are observed in pediatric RSV-induced lung injury. Crit Care Med 40:1-328.
184. Schuurhof A, Bont L, Hodemaekers HM, de Klerk A, de Groot H, Hofland RW, van de Pol AC, Kimpen JL, Janssen R. 2012. Proteins involved in extracellular matrix dynamics are associated with respiratory syncytial virus disease severity. Eur Respir J 39:1475-1481. https://doi.org/10.1183/09031936.00012311.
185. Kawasaki Y, Aoyagi Y, Abe Y, Go H, Imamura T, Kaneko M, Ito M, Katayose M, Hashimoto K, Hosoya M. 2009. Serum KL-6 levels as a biomarker of lung injury in respiratory syncytial virus bronchiolitis. J Med Virol 81:2104-2108. https://doi.org/10.1002/jmv.21634.
186. Bem RA, Bos AP, Wosten-van Asperen RM, Bruijn M, Lutter R, Sprick MR, van Woensel JB. 2010. Potential role of soluble TRAIL in epithelial injury in children with severe RSV infection. Am J Respir Cell Mol Biol 42: 697-705. https://doi.org/10.1165/rcmb.2009-0100OC.