The lung Microbiome, immunity, and the pathogenesis of chronic lung disease

Journal of Immunology

Volumn 196, Issue 12, 2016, Pages 4839-4847

  O'Dwyer, David N ^a   Dickson, Robert P ^a   Moore, Bethany B ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ASTHMA; BACTERIAL GROWTH; CHRONIC LUNG DISEASE; CHRONIC OBSTRUCTIVE LUNG DISEASE; CYSTIC FIBROSIS; DISEASE ASSOCIATION; DISEASE EXACERBATION; DISEASE PREDISPOSITION; EVIDENCE BASED MEDICINE; FIBROSING ALVEOLITIS; HOST PATHOGEN INTERACTION; HOST RESISTANCE; HUMAN; IMMUNITY; IMMUNOGENICITY; IMMUNOREGULATION; INNATE IMMUNITY; LUNG; LUNG MICROBIOME; LUNG STERILITY; METHODOLOGY; MICROBIOME; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; SPECIES COMPOSITION; BACTERIUM; CHRONIC DISEASE; CLASSIFICATION; DISEASE COURSE; DYSBIOSIS; GENETICS; GROWTH, DEVELOPMENT AND AGING; HOMEOSTASIS; IMMUNOLOGY; ISOLATION AND PURIFICATION; LUNG DISEASE; MICROBIOLOGY; MICROFLORA; PATHOPHYSIOLOGY; PHYSIOLOGY;

BACTERIA; CHRONIC DISEASE; DISEASE PROGRESSION; DYSBIOSIS; HOMEOSTASIS; HOST-PATHOGEN INTERACTIONS; HUMANS; LUNG; LUNG DISEASES; MICROBIOTA;

EID: 84974777845     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1600279     Document Type: Review

References (126)

1. Lederberg, J., and A. T. McCray. 2001. Ome sweet omics-A genealogical treasury of words. Scientist 15: 8.
2. Bauer, H., R. E. Horowitz, S. M. Levenson, and H. Popper. 1963. The response of the lymphatic tissue to the microbial flora. Studies on germfree mice. Am. J. Pathol. 42: 471-483.
3. Naik, S., N. Bouladoux, C. Wilhelm, M. J. Molloy, R. Salcedo, W. Kastenmuller, C. Deming, M. Quinones, L. Koo, S. Conlan, et al. 2012. Compartmentalized control of skin immunity by resident commensals. Science 337: 1115-1119.
4. Noverr, M. C., R. M. Noggle, G. B. Toews, and G. B. Huffnagle. 2004. Role of antibiotics and fungal microbiota in driving pulmonary allergic responses. Infect. Immun. 72: 4996-5003.
5. Manuzak, J. A., T. Hensley-McBain, A. S. Zevin, C. Miller, R. Cubas, B. Agricola, J. Gile, L. Richert-Spuhler, G. Patilea, J. D. Estes, et al. 2016.Enhancement of microbiota in healthy macaques results in beneficial modulation of mucosal and systemic immune function. J. Immunol. 196: 2401-2409.
6. Block, K. E., Z. Zheng, A. L. Dent, B. L. Kee, and H. Huang. 2016. Gut microbiota regulates K/BxN autoimmune arthritis through follicular helper T but not Th17 cells. J. Immunol. 196: 1550-1557.
7. Ishizaki, Y., M. Takemoto, R. Kira, K. Kusuhara, H. Torisu, Y. Sakai, M. Sanefuji, N. Yukaya, and T. Hara. 2008. Association of Toll-like receptor 3 gene polymorphism with subacute sclerosing panencephalitis. J. Neurovirol. 14: 486-491.
8. Netea, M. G., C. Wijmenga, and L. A. ONeill. 2012. Genetic variation in Tolllike receptors and disease susceptibility. Nat. Immunol. 13: 535-542.
9. Khor, C. C., S. J. Chapman, F. O. Vannberg, A. Dunne, C. Murphy, E. Y. Ling, A. J. Frodsham, A. J. Walley, O. Kyrieleis, A. Khan, et al. 2007. A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis. Nat. Genet. 39: 523-528.
10. Dickson, R. P., J. R. Erb-Downward, F. J. Martinez, and G. B. Huffnagle. 2016. The microbiome and the respiratory tract. Annu. Rev. Physiol. 78: 481-504.
11. Caballero, S., and E. G. Pamer. 2015. Microbiota-mediated inflammation and antimicrobial defense in the intestine. Annu. Rev. Immunol. 33: 227-256.
12. Martin, C., P. R. Burgel, P. Lepage, C. Andréjak, J. de Blic, A. Bourdin, J. Brouard, P. Chanez, J. C. Dalphin, G. Deslée, et al. 2015. Host-microbe interactions in distal airways: relevance to chronic airway diseases. Eur. Respir. Rev. 24: 78-91.
13. Winslow, C. E. 1908. A new method of enumerating bacteria in air. Science 28: 28-31.
14. Thomas, D. N., and G. S. Dieckmann. 2002. Antarctic Sea ice-A habitat for extremophiles. Science 295: 641-644.
15. Yamamoto, H., A. Hiraishi, K. Kato, H. X. Chiura, Y. Maki, and A. Shimizu. 1998. Phylogenetic evidence for the existence of novel thermophilic bacteria in hot spring sulfur-Turf microbial mats in Japan. Appl. Environ. Microbiol. 64: 1680-1687.
16. Wilson, M. T., and D. L. Hamilos. 2014. The nasal and sinus microbiome in health and disease. Curr. Allergy Asthma Rep. 14: 485.
17. Gleeson, K., D. F. Eggli, and S. L. Maxwell. 1997. Quantitative aspiration during sleep in normal subjects. Chest 111: 1266-1272.
18. Huxley, E. J., J. Viroslav, W. R. Gray, and A. K. Pierce. 1978. Pharyngeal aspiration in normal adults and patients with depressed consciousness. Am. J. Med. 64: 564-568.
19. Dickson, R. P., J. R. Erb-Downward, C. M. Freeman, L. McCloskey, J. M. Beck, G. B. Huffnagle, and J. L. Curtis. 2015. Spatial variation in the healthy human lung microbiome and the adapted island model of lung biogeography. Ann. Am. Thorac. Soc. 12: 821-830.
20. Hilty, M., C. Burke, H. Pedro, P. Cardenas, A. Bush, C. Bossley, J. Davies, A. Ervine, L. Poulter, L. Pachter, et al. 2010. Disordered microbial communities in asthmatic airways. PLoS One 5: e8578.
21. Morris, A., J. M. Beck, P. D. Schloss, T. B. Campbell, K. Crothers, J. L. Curtis, S. C. Flores, A. P. Fontenot, E. Ghedin, L. Huang, et al; Lung HIV Microbiome Project. 2013. Comparison of the respiratory microbiome in healthy nonsmokers and smokers. Am. J. Respir. Crit. Care Med. 187: 1067-1075.
22. Bassis, C. M., J. R. Erb-Downward, R. P. Dickson, C. M. Freeman, T. M. Schmidt, V. B. Young, J. M. Beck, J. L. Curtis, and G. B. Huffnagle. 2015. Analysis of the upper respiratory tract microbiotas as the source of the lung and gastric microbiotas in healthy individuals. MBio 6: e00037.
23. Dickson, R. P., J. R. Erb-Downward, C. M. Freeman, N. Walker, B. S. Scales, J. M. Beck, F. J. Martinez, J. L. Curtis, V. N. Lama, and G. B. Huffnagle. 2014. Changes in the lung microbiome following lung transplantation include the emergence of two distinct Pseudomonas species with distinct clinical associations. PLoS One 9: e97214.
24. Segal, L. N., A. V. Alekseyenko, J. C. Clemente, R. Kulkarni, B. Wu, Z. Gao, H. Chen, K. I. Berger, R. M. Goldring, W. N. Rom, et al. 2013. Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation. Microbiome 1: 19.
25. Rogers, G. B., D. Shaw, R. L. Marsh, M. P. Carroll, D. J. Serisier, and K. D. Bruce. 2015. Respiratory microbiota: Addressing clinical questions, informing clinical practice. Thorax 70: 74-81.
26. Zhu, B., D. Xiao, H. Zhang, Y. Zhang, Y. Gao, L. Xu, J. Lv, Y. Wang, J. Zhang, and Z. Shao. 2013. MALDI-TOF MS distinctly differentiates nontypable Haemophilus influenzae from Haemophilus haemolyticus. PLoS One 8: e56139.
27. OToole, P. W., and I. B. Jeffery. 2015. Gut microbiota and aging. Science 350: 1214-1215.
28. David, L. A., C. F. Maurice, R. N. Carmody, D. B. Gootenberg, J. E. Button, B. E. Wolfe, A. V. Ling, A. S. Devlin, Y. Varma, M. A. Fischbach, et al. 2014. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505: 559-563.
29. Mason, M. R., H. N. Nagaraja, T. Camerlengo, V. Joshi, and P. S. Kumar. 2013. Deep sequencing identifies ethnicity-specific bacterial signatures in the oral microbiome. PLoS One 8: e77287.
30. Shah, N., H. Tang, T. G. Doak, and Y. Ye. 2011. Comparing bacterial communities inferred from 16S rRNA gene sequencing and shotgun metagenomics. Pac. Symp. Biocomput. 2011: 165-176.
31. Eckburg, P. B., E. M. Bik, C. N. Bernstein, E. Purdom, L. Dethlefsen, M. Sargent, S. R. Gill, K. E. Nelson, and D. A. Relman. 2005. Diversity of the human intestinal microbial flora. Science 308: 1635-1638.
32. Grice, E. A., and J. A. Segre. 2011. The skin microbiome. Nat. Rev. Microbiol. 9: 244-253.
33. Frank, D. N., L. M. Feazel, M. T. Bessesen, C. S. Price, E. N. Janoff, and N. R. Pace. 2010. The human nasal microbiota and Staphylococcus aureus carriage. PLoS One 5: e10598.
34. Kim, T. K., S. M. Thomas, M. Ho, S. Sharma, C. I. Reich, J. A. Frank, K. M. Yeater, D. R. Biggs, N. Nakamura, R. Stumpf, et al. 2009. Heterogeneity of vaginal microbial communities within individuals. J. Clin. Microbiol. 47: 1181-1189.
35. Gollwitzer, E. S., S. Saglani, A. Trompette, K. Yadava, R. Sherburn, K. D. McCoy, L. P. Nicod, C. M. Lloyd, and B. J. Marsland. 2014. Lung microbiota promotes tolerance to allergens in neonates via PD-L1. Nat. Med. 20: 642-647.
36. Dominguez-Bello, M. G., E. K. Costello, M. Contreras, M. Magris, G. Hidalgo, N. Fierer, and R. Knight. 2010. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc. Natl. Acad. Sci. USA 107: 11971-11975.
37. Yatsunenko, T., F. E. Rey, M. J. Manary, I. Trehan, M. G. Dominguez-Bello, M. Contreras, M. Magris, G. Hidalgo, R. N. Baldassano, A. P. Anokhin, et al. 2012. Human gut microbiome viewed across age and geography. Nature 486: 222-227.
38. Biesbroek, G., E. Tsivtsivadze, E. A. Sanders, R. Montijn, R. H. Veenhoven, B. J. Keijser, and D. Bogaert. 2014. Early respiratory microbiota composition determines bacterial succession patterns and respiratory health in children. Am. J. Respir. Crit. Care Med. 190: 1283-1292.
39. Erb-Downward, J. R., D. L. Thompson, M. K. Han, C. M. Freeman, L. McCloskey, L. A. Schmidt, V. B. Young, G. B. Toews, J. L. Curtis, B. Sundaram, et al. 2011. Analysis of the lung microbiome in the "healthy" smoker and in COPD. PLoS One 6: e16384.
40. Charlson, E. S., J. M. Diamond, K. Bittinger, A. S. Fitzgerald, A. Yadav, A. R. Haas, F. D. Bushman, and R. G. Collman. 2012. Lung-enriched organisms and aberrant bacterial and fungal respiratory microbiota after lung transplant. Am. J. Respir. Crit. Care Med. 186: 536-545.
41. Sze, M. A., P. A. Dimitriu, S. Hayashi, W. M. Elliott, J. E. McDonough, J. V. Gosselink, J. Cooper, D. D. Sin, W. W. Mohn, and J. C. Hogg. 2012. The lung tissue microbiome in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 185: 1073-1080.
42. Ingenito, E. P., J. Solway, E. R. McFadden, Jr., B. Pichurko, H. F. Bowman, D. Michaels, and J. M. Drazen. 1987. Indirect assessment of mucosal surface temperatures in the airways: Theory and tests. J. Appl. Physiol. 63: 2075-2083.
43. West, J. B. 1978. Regional differences in the lung. Chest 74: 426-437.
44. Nishimura, K., M. Kitaichi, T. Izumi, S. Nagai, M. Kanaoka, and H. Itoh. 1992. Usual interstitial pneumonia: histologic correlation with high-resolution CT. Radiology 182: 337-342.
45. Collawn, J. F., and S. Matalon. 2014. CFTR and lung homeostasis. Am. J. Physiol. Lung Cell. Mol. Physiol. 307: L917-L923.
46. Raghu, G., T. D. Freudenberger, S. Yang, J. R. Curtis, C. Spada, J. Hayes, J. K. Sillery, C. E. Pope, II, and C. A. Pellegrini. 2006. High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis. Eur. Respir. J. 27: 136-142.
47. Robinson, N. B., and E. DiMango. 2014. Prevalence of gastroesophageal reflux in cystic fibrosis and implications for lung disease. Ann. Am. Thorac. Soc. 11: 964-968.
48. Ryerson, C. J., V. Cottin, K. K. Brown, and H. R. Collard. 2015. Acute exacerbation of idiopathic pulmonary fibrosis: shifting the paradigm. Eur. Respir. J. 46: 512-520.
49. Monsó, E., J. Ruiz, A. Rosell, J. Manterola, J. Fiz, J. Morera, and V. Ausina. 1995. Bacterial infection in chronic obstructive pulmonary disease. A study of stable and exacerbated outpatients using the protected specimen brush. Am. J. Respir. Crit. Care Med. 152: 1316-1320.
50. Sethi, S., R. Sethi, K. Eschberger, P. Lobbins, X. Cai, B. J. Grant, and T. F. Murphy. 2007. Airway bacterial concentrations and exacerbations of chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 176: 356-361.
51. Vollenweider, D. J., H. Jarrett, C. A. Steurer-Stey, J. Garcia-Aymerich, and M. A. Puhan. 2012. Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. 12: CD010257.
52. Millares, L., R. Ferrari, M. Gallego, M. Garcia-Nunez, V. Pérez-Brocal, M. Espasa, X. Pomares, C. Monton, A. Moya, and E. Monsó. 2014. Bronchial microbiome of severe COPD patients colonised by Pseudomonas aeruginosa. Eur. J. Clin. Microbiol. Infect. Dis. 33: 1101-1111.
53. Huang, Y. J., S. Sethi, T. Murphy, S. Nariya, H. A. Boushey, and S. V. Lynch. 2014. Airway microbiome dynamics in exacerbations of chronic obstructive pulmonary disease. J. Clin. Microbiol. 52: 2813-2823.
54. Pragman, A. A., H. B. Kim, C. S. Reilly, C. Wendt, and R. E. Isaacson. 2012. The lung microbiome in moderate and severe chronic obstructive pulmonary disease. PLoS One 7: e47305.
55. Hewitt, R., H. Farne, A. Ritchie, E. Luke, S. L. Johnston, and P. Mallia. 2016. The role of viral infections in exacerbations of chronic obstructive pulmonary disease and asthma. Ther. Adv. Respir. Dis. 10: 158-174.
56. Papi, A., C. M. Bellettato, F. Braccioni, M. Romagnoli, P. Casolari, G. Caramori, L. M. Fabbri, and S. L. Johnston. 2006. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am. J. Respir. Crit. Care Med. 173: 1114-1121.
57. Rohde, G., A.Wiethege, I. Borg, M. Kauth, T. T. Bauer, A. Gillissen, A. Bufe, and G. Schultze-Werninghaus. 2003. Respiratory viruses in exacerbations of chronic obstructive pulmonary disease requiring hospitalisation: A case-control study. Thorax 58: 37-42.
58. Mallia, P., S. D. Message, V. Gielen, M. Contoli, K. Gray, T. Kebadze, J. Aniscenko, V. Laza-Stanca, M. R. Edwards, L. Slater, et al. 2011. Experimental rhinovirus infection as a human model of chronic obstructive pulmonary disease exacerbation. Am. J. Respir. Crit. Care Med. 183: 734-742.
59. Seemungal, T., R. Harper-Owen, A. Bhowmik, I. Moric, G. Sanderson, S. Message, P. Maccallum, T. W. Meade, D. J. Jeffries, S. L. Johnston, and J. A. Wedzicha. 2001. Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 164: 1618-1623.
60. Molyneaux, P. L., P. Mallia, M. J. Cox, J. Footitt, S. A. Willis-Owen, D. Homola, M. B. Trujillo-Torralbo, S. Elkin, O. M. Kon, W. O. Cookson, et al. 2013. Outgrowth of the bacterial airway microbiome after rhinovirus exacerbation of chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 188: 1224-1231.
61. Mortaz, E., I. M. Adcock, F. L. Ricciardolo, M. Varahram, H. Jamaati, A. A. Velayati, G. Folkerts, and J. Garssen. 2015. Anti-Inflammatory Effects of Lactobacillus rahmnosus and Bifidobacterium breve on cigarette smoke activated human macrophages. PLoS One 10: e0136455.
62. Tomosada, Y., E. Chiba, H. Zelaya, T. Takahashi, K. Tsukida, H. Kitazawa, S. Alvarez, and J. Villena. 2013. Nasally administered Lactobacillus rhamnosus strains differentially modulate respiratory antiviral immune responses and induce protection against respiratory syncytial virus infection. BMC Immunol. 14: 40.
63. Marri, P. R., D. A. Stern, A. L. Wright, D. Billheimer, and F. D. Martinez. 2013. Asthma-Associated differences in microbial composition of induced sputum. J. Allergy Clin. Immunol. 131: 346-352.e1-3.
64. Huang, Y. J., C. E. Nelson, E. L. Brodie, T. Z. Desantis, M. S. Baek, J. Liu, T. Woyke, M. Allgaier, J. Bristow, J. P. Wiener-Kronish, et al; National Heart, Lung, and Blood Institutes Asthma Clinical Research Network. 2011. Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma. J. Allergy Clin. Immunol. 127: 372-381.e1-3.
65. Gonem, S., I. Umar, D. Burke, D. Desai, S. Corkill, J. Owers-Bradley, C. E. Brightling, and S. Siddiqui. 2012. Airway impedance entropy and exacerbations in severe asthma. Eur. Respir. J. 40: 1156-1163.
66. Nicholson, K. G., J. Kent, and D. C. Ireland. 1993. Respiratory viruses and exacerbations of asthma in adults. BMJ 307: 982-986.
67. Johnston, S. L., P. K. Pattemore, G. Sanderson, S. Smith, F. Lampe, L. Josephs, P. Symington, S. OToole, S. H. Myint, D. A. Tyrrell, et al. 1995. Community study of role of viral infections in exacerbations of asthma in 9-11 year old children. BMJ 310: 1225-1229.
68. Ege, M. J., M. Mayer, A. C. Normand, J. Genuneit, W. O. Cookson, C. Braun-Fahrländer, D. Heederik, R. Piarroux, and E. von Mutius, GABRIELA Transregio 22 Study Group. 2011. Exposure to environmental microorganisms and childhood asthma. N. Engl. J. Med. 364: 701-709.
69. Trompette, A., E. S. Gollwitzer, K. Yadava, A. K. Sichelstiel, N. Sprenger, C. Ngom-Bru, C. Blanchard, T. Junt, L. P. Nicod, N. L. Harris, and B. J. Marsland. 2014. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat. Med. 20: 159-166.
70. Lemaire, M. M., L. Dumoutier, G. Warnier, C. Uyttenhove, J. Van Snick, M. de Heusch, M. Stevens, and J. C. Renauld. 2011. Dual TCR expression biases lung inflammation in DO11.10 transgenic mice and promotes neutrophilia via microbiota-induced Th17 differentiation. J. Immunol. 187: 3530-3537.
71. Russell, S. L., M. J. Gold, B. P. Willing, L. Thorson, K. M. McNagny, and B. B. Finlay. 2013. Perinatal antibiotic treatment affects murine microbiota, immune responses and allergic asthma. Gut Microbes 4: 158-164.
72. Raghu, G., B. Rochwerg, Y. Zhang, C. A. Garcia, A. Azuma, J. Behr, J. L. Brozek, H. R. Collard, W. Cunningham, S. Homma, et al; American Thoracic Society; European Respiratory society; Japanese Respiratory Society; Latin American Thoracic Association. 2015. An official ATS/ERS/JRS/ALAT clinical practice guideline: Treatment of idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline. Am. J. Respir. Crit. Care Med. 192: e3-e19.
73. Knippenberg, S., B. Ueberberg, R. Maus, J. Bohling, N. Ding, M. Tort Tarres, H. G. Hoymann, D. Jonigk, N. Izykowski, J. C. Paton, et al. 2015. Streptococcus pneumoniae triggers progression of pulmonary fibrosis through pneumolysin. Thorax 70: 636-646.
74. Lasithiotaki, I., K. M. Antoniou, V. M. Vlahava, K. Karagiannis, D. A. Spandidos, N. M. Siafakas, and G. Sourvinos. 2011. Detection of herpes simplex virus type-1 in patients with fibrotic lung diseases. PLoS One 6: e27800.
75. Pulkkinen, V., S. Bruce, J. Rintahaka, U. Hodgson, T. Laitinen, H. Alenius, V. L. Kinnula, M. Myllärniemi, S. Matikainen, and J. Kere. 2010. ELMOD2, a candidate gene for idiopathic pulmonary fibrosis, regulates antiviral responses. FASEB J. 24: 1167-1177.
76. Molyneaux, P. L., M. J. Cox, S. A. Willis-Owen, P. Mallia, K. E. Russell, A. M. Russell, E. Murphy, S. L. Johnston, D. A. Schwartz, A. U. Wells, et al. 2014. The role of bacteria in the pathogenesis and progression of idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 190: 906-913.
77. Folcik, V. A., M. Garofalo, J. Coleman, J. J. Donegan, E. Rabbani, S. Suster, A. Nuovo, C. M. Magro, G. Di Leva, and G. J. Nuovo. 2014. Idiopathic pulmonary fibrosis is strongly associated with productive infection by herpesvirus saimiri. Mod. Pathol. 27: 851-862.
78. Collard, H. R., B. B. Moore, K. R. Flaherty, K. K. Brown, R. J. Kaner, T. E. King, Jr., J. A. Lasky, J. E. Loyd, I. Noth, M. A. Olman, et al; Idiopathic Pulmonary Fibrosis Clinical Research Network Investigators. 2007. Acute exacerbations of idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 176: 636-643.
79. Han, M. K., Y. Zhou, S. Murray, N. Tayob, I. Noth, V. N. Lama, B. B. Moore, E. S. White, K. R. Flaherty, G. B. Huffnagle, and F. J. Martinez, COMET Investigators. 2014. Lung microbiome and disease progression in idiopathic pulmonary fibrosis: An analysis of the COMET study. Lancet Respir. Med. 2: 548-556.
80. Varney, V. A., H. M. Parnell, D. T. Salisbury, S. Ratnatheepan, and R. B. Tayar. 2008. A double blind randomised placebo controlled pilot study of oral cotrimoxazole in advanced fibrotic lung disease. Pulm. Pharmacol. Ther. 21: 178-187.
81. ODwyer, D. N., M. E. Armstrong, G. Trujillo, G. Cooke, M. P. Keane, P. G. Fallon, A. J. Simpson, A. B. Millar, E. E. McGrath, M. K. Whyte, et al. 2013. The Toll-like receptor 3 L412F polymorphism and disease progression in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 188: 1442-1450.
82. Trujillo, G., A. Meneghin, K. R. Flaherty, L. M. Sholl, J. L. Myers, E. A. Kazerooni, B. H. Gross, S. R. Oak, A. L. Coelho, H. Evanoff, et al. 2010. TLR9 differentiates rapidly from slowly progressing forms of idiopathic pulmonary fibrosis. Sci. Transl. Med. 2: 57ra82.
83. Lafyatis, R., and A. Farina. 2012. New insights into the mechanisms of innate immune receptor signalling in fibrosis. Open Rheumatol. J. 6: 72-79.
84. Margaritopoulos, G. A., K. M. Antoniou, K. Karagiannis, K. D. Samara, I. Lasithiotaki, E. Vassalou, R. Lymbouridou, H. Koutala, and N. M. Siafakas. 2010. Investigation of Toll-like receptors in the pathogenesis of fibrotic and granulomatous disorders: A bronchoalveolar lavage study. Fibrogenesis Tissue Repair 3: 20.
85. Papanikolaou, I. C., K. A. Boki, E. J. Giamarellos-Bourboulis, A. Kotsaki, K. Kagouridis, N. Karagiannidis, and V. S. Polychronopoulos. 2015. Innate immunity alterations in idiopathic interstitial pneumonias and rheumatoid arthritisassociated interstitial lung diseases. Immunol. Lett. 163: 179-186.
86. Samara, K. D., K. M. Antoniou, K. Karagiannis, G. Margaritopoulos, I. Lasithiotaki, E. Koutala, and N. M. Siafakas. 2012. Expression profiles of Tolllike receptors in non-small cell lung cancer and idiopathic pulmonary fibrosis. Int. J. Oncol. 40: 1397-1404.
87. Stenbit, A. E., and P. A. Flume. 2011. Pulmonary exacerbations in cystic fibrosis. Curr. Opin. Pulm. Med. 17: 442-447.
88. Ramsey, B. W. 1996. Management of pulmonary disease in patients with cystic fibrosis. N. Engl. J. Med. 335: 179-188.
89. Gold, R., S. Carpenter, H. Heurter, M. Corey, and H. Levison. 1987. Randomized trial of ceftazidime versus placebo in the management of acute respiratory exacerbations in patients with cystic fibrosis. J. Pediatr. 111: 907-913.
90. Hurley, M. N., A. H. Ariff, C. Bertenshaw, J. Bhatt, and A. R. Smyth. 2012. Results of antibiotic susceptibility testing do not influence clinical outcome in children with cystic fibrosis. J. Cyst. Fibros. 11: 288-292.
91. Smith, A. L., S. B. Fiel, N. Mayer-Hamblett, B. Ramsey, and J. L. Burns. 2003. Susceptibility testing of Pseudomonas aeruginosa isolates and clinical response to parenteral antibiotic administration: lack of association in cystic fibrosis. Chest 123: 1495-1502.
92. Price, K. E., T. H. Hampton, A. H. Gifford, E. L. Dolben, D. A. Hogan, H. G. Morrison, M. L. Sogin, and G. A. OToole. 2013. Unique microbial communities persist in individual cystic fibrosis patients throughout a clinical exacerbation. Microbiome 1: 27.
93. Carmody, L. A., J. Zhao, P. D. Schloss, J. F. Petrosino, S. Murray, V. B. Young, J. Z. Li, and J. J. LiPuma. 2013. Changes in cystic fibrosis airway microbiota at pulmonary exacerbation. Ann. Am. Thorac. Soc. 10: 179-187.
94. Stressmann, F. A., G. B. Rogers, P. Marsh, A. K. Lilley, T. W. Daniels, M. P. Carroll, L. R. Hoffman, G. Jones, C. E. Allen, N. Patel, et al. 2011. Does bacterial density in cystic fibrosis sputum increase prior to pulmonary exacerbation? J. Cyst. Fibros. 10: 357-365.
95. Cox, M. J., M. Allgaier, B. Taylor, M. S. Baek, Y. J. Huang, R. A. Daly, U. Karaoz, G. L. Andersen, R. Brown, K. E. Fujimura, et al. 2010. Airway microbiota and pathogen abundance in age-stratified cystic fibrosis patients. PLoS One 5: e11044.
96. Zhao, J., P. D. Schloss, L. M. Kalikin, L. A. Carmody, B. K. Foster, J. F. Petrosino, J. D. Cavalcoli, D. R. VanDevanter, S. Murray, J. Z. Li, et al. 2012. Decade-long bacterial community dynamics in cystic fibrosis airways. Proc. Natl. Acad. Sci. USA 109: 5809-5814.
97. Aitken, M. L., A. Limaye, P. Pottinger, E. Whimbey, C. H. Goss, M. R. Tonelli, G. A. Cangelosi, M. A. Dirac, K. N. Olivier, B. A. Brown-Elliott, et al. 2012. Respiratory outbreak of Mycobacterium abscessus subspecies massiliense in a lung transplant and cystic fibrosis center. Am. J. Respir. Crit. Care Med. 185: 231-232.
98. Esther, C. R., Jr., D. A. Esserman, P. Gilligan, A. Kerr, and P. G. Noone. 2010. Chronic Mycobacterium abscessus infection and lung function decline in cystic fibrosis. J. Cyst. Fibros. 9: 117-123.
99. Sanguinetti, M., F. Ardito, E. Fiscarelli, M. La Sorda, P. DArgenio, G. Ricciotti, and G. Fadda. 2001. Fatal pulmonary infection due to multidrug-resistant Mycobacterium abscessus in a patient with cystic fibrosis. J. Clin. Microbiol. 39: 816-819.
100. Floto, R. A., K. N. Olivier, L. Saiman, C. L. Daley, J. L. Herrmann, J. A. Nick, P. G. Noone, D. Bilton, P. Corris, R. L. Gibson, et al. 2016. US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-Tuberculous mycobacteria in individuals with cystic fibrosis. Thorax 71(Suppl. 1): i1-i22.
101. Clarke, T. B. 2014. Early innate immunity to bacterial infection in the lung is regulated systemically by the commensal microbiota via Nod-like receptor ligands. Infect. Immun. 82: 4596-4606.
102. Sassone-Corsi, M., and M. Raffatellu. 2015. No vacancy: how beneficial microbes cooperate with immunity to provide colonization resistance to pathogens. J. Immunol. 194: 4081-4087.
103. Savage, D. C. 1977. Microbial ecology of the gastrointestinal tract. Annu. Rev. Microbiol. 31: 107-133.
104. Arumugam, M., J. Raes, E. Pelletier, D. Le Paslier, T. Yamada, D. R. Mende, G. R. Fernandes, J. Tap, T. Bruls, J. M. Batto, et al; MetaHIT Consortium. 2011. Enterotypes of the human gut microbiome. Nature 473: 174-180.
105. Abrahamsson, T. R., H. E. Jakobsson, A. F. Andersson, B. Björkstén, L. Engstrand, and M. C. Jenmalm. 2012. Low diversity of the gut microbiota in infants with atopic eczema. J. Allergy Clin. Immunol. 129: 434-440, 440.e1-440. e2.
106. Bruzzese, E., M. L. Callegari, V. Raia, S. Viscovo, R. Scotto, S. Ferrari, L. Morelli, V. Buccigrossi, A. Lo Vecchio, E. Ruberto, and A. Guarino. 2014. Disrupted intestinal microbiota and intestinal inflammation in children with cystic fibrosis and its restoration with Lactobacillus GG: A randomised clinical trial. PLoS One 9: e87796.
107. Inagaki, H., T. Suzuki, K. Nomoto, and Y. Yoshikai. 1996. Increased susceptibility to primary infection with Listeria monocytogenes in germfree mice may be due to lack of accumulation of L-selectin+ CD44+ T cells in sites of inflammation. Infect. Immun. 64: 3280-3287.
108. Fagundes, C. T., F. A. Amaral, A. T. Vieira, A. C. Soares, V. Pinho, J. R. Nicoli, L. Q. Vieira, M. M. Teixeira, and D. G. Souza. 2012. Transient TLR activation restores inflammatory response and ability to control pulmonary bacterial infection in germfree mice. J. Immunol. 188: 1411-1420.
109. Abt, M. C., L. C. Osborne, L. A. Monticelli, T. A. Doering, T. Alenghat, G. F. Sonnenberg, M. A. Paley, M. Antenus, K. L. Williams, J. Erikson, et al. 2012. Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity 37: 158-170.
110. Clarke, T. B., K. M. Davis, E. S. Lysenko, A. Y. Zhou, Y. Yu, and J. N. Weiser. 2010. Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity. Nat. Med. 16: 228-231.
111. MacDonald, M., T. Korman, P. King, K. Hamza, and P. Bardin. 2013. Exacerbation phenotyping in chronic obstructive pulmonary disease. Respirology 18: 1280-1281.
112. Jaspers, I. 2014. Cigarette smoke effects on innate immune mechanisms in the nasal mucosa. Potential effects on the microbiome. Ann. Am. Thorac. Soc. 11 (Suppl. 1): S38-S42.
113. Wang, J., F. Li, H. Wei, Z. X. Lian, R. Sun, and Z. Tian. 2014. Respiratory influenza virus infection induces intestinal immune injury via microbiota-mediated Th17 cell-dependent inflammation. J. Exp. Med. 211: 2397-2410.
114. Chewning, J. H., and C. T. Weaver. 2014. Development and survival of Th17 cells within the intestines: The influence of microbiome-And diet-derived signals. J. Immunol. 193: 4769-4777.
115. Tan, H. L., and M. Rosenthal. 2013. IL-17 in lung disease: friend or foe? Thorax 68: 788-790.
116. Kudo, M., A. C. Melton, C. Chen, M. B. Engler, K. E. Huang, X. Ren, Y. Wang, X. Bernstein, J. T. Li, K. Atabai, et al. 2012. IL-17A produced by ab T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction. Nat. Med. 18: 547-554.
117. Tan, H. L., N. Regamey, S. Brown, A. Bush, C. M. Lloyd, and J. C. Davies. 2011. The Th17 pathway in cystic fibrosis lung disease. Am. J. Respir. Crit. CareMed. 184: 252-258.
118. Facco, M., A. Cabrelle, A. Teramo, V. Olivieri, M. Gnoato, S. Teolato, E. Ave, C. Gattazzo, G. P. Fadini, F. Calabrese, et al. 2011. Sarcoidosis is a Th1/Th17 multisystem disorder. Thorax 66: 144-150.
119. Vanaudenaerde, B. M., S. I. De Vleeschauwer, R. Vos, I. Meyts, D. M. Bullens, V. Reynders, W. A. Wuyts, D. E. Van Raemdonck, L. J. Dupont, and G. M. Verleden. 2008. The role of the IL23/IL17 axis in bronchiolitis obliterans syndrome after lung transplantation. Am. J. Transplant. 8: 1911-1920.
120. Zhou, X., H. Loomis-King, S. J. Gurczynski, C. A. Wilke, K. E. Konopka, C. Ptaschinski, S. M. Coomes, Y. Iwakura, L. F. van Dyk, N. W. Lukacs, and B. B. Moore. 2015. Bone marrow transplantation alters lung antigen-presenting cells to promote TH17 response and the development of pneumonitis and fibrosis following gammaherpesvirus infection. Mucosal Immunol. In press.
121. Yadava, K., C. Pattaroni, A. K. Sichelstiel, A. Trompette, E. S. Gollwitzer, O. Salami, C. von Garnier, L. P. Nicod, and B. J. Marsland. 2015. Microbiota promotes chronic pulmonary inflammation by enhancing IL-17A and autoantibodies. Am. J. Respir. Crit. Care Med. In press.
122. Tan, Z., X. Qian, R. Jiang, Q. Liu, Y. Wang, C. Chen, X. Wang, B. Ryffel, and B. Sun. 2013. IL-17A plays a critical role in the pathogenesis of liver fibrosis through hepatic stellate cell activation. J. Immunol. 191: 1835-1844.
123. Wilson, M. S., S. K. Madala, T. R. Ramalingam, B. R. Gochuico, I. O. Rosas, A. W. Cheever, and T. A. Wynn. 2010. Bleomycin and IL-1b-mediated pulmonary fibrosis is IL-17A dependent. J. Exp. Med. 207: 535-552.
124. Ray, S., C. De Salvo, and T. T. Pizarro. 2014. Central role of IL-17/Th17 immune responses and the gut microbiota in the pathogenesis of intestinal fibrosis. Curr. Opin. Gastroenterol. 30: 531-538.
125. Atarashi, K., T. Tanoue, M. Ando, N. Kamada, Y. Nagano, S. Narushima, W. Suda, A. Imaoka, H. Setoyama, T. Nagamori, et al. 2015. Th17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell 163: 367-380.
126. Gauguet, S., S. DOrtona, K. Ahnger-Pier, B. Duan, N. K. Surana, R. Lu, C. Cywes-Bentley, M. Gadjeva, Q. Shan, G. P. Priebe, and G. B. Pier. 2015. Intestinal microbiota of mice influences resistance to Staphylococcus aureus pneumonia. Infect. Immun. 83: 4003-4014.