Fungal Exposure and Asthma: IgE and Non-IgE-Mediated Mechanisms

Current Allergy and Asthma Reports

Volumn 16, Issue 12, 2016, Pages

  Zhang, Zhonghua ^a   Reponen, Tiina ^b   Hershey, Gurjit K Khurana ^a,b  

^a CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

^b UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

Author keywords

Asthma; Childhood asthma; Exposure; Fungi; Mold

Indexed keywords

BETA 1,3 GLUCAN; CELLULOSE; CHITIN; DAMAGE ASSOCIATED MOLECULAR PATTERN; DECTIN 1; EOTAXIN; GAMMA INTERFERON; IMMUNOGLOBULIN E; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 17; INTERLEUKIN 1ALPHA; INTERLEUKIN 20; INTERLEUKIN 6; INTERLEUKIN 8; JANUS KINASE; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MACROPHAGE INFLAMMATORY PROTEIN 2; MACROPHAGE INFLAMMATORY PROTEIN 3ALPHA; PATHOGEN ASSOCIATED MOLECULAR PATTERN; PATTERN RECOGNITION RECEPTOR; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHOLIPASE C; PROTEIN KINASE B; PROTEIN P53; STAT PROTEIN; THYMUS AND ACTIVATION REGULATED CHEMOKINE; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG; UNINDEXED DRUG;

AIRWAY SMOOTH MUSCLE CELL; ASPERGILLUS FUMIGATUS; ASPERGILLUS VERSICOLOR; ASTHMA; CANDIDA ALBICANS; CLADOSPORIUM HERBARUM; DISEASE EXACERBATION; DISEASE SEVERITY; DRY WEIGHT; ENZYME IMMUNOASSAY; EPICOCCUM NIGRUM; EXTRACELLULAR MATRIX; FUNGAL BIOMASS; FUNGAL CELL WALL; FUNGAL SPORE GERMINATION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; IMMUNOCOMPROMISED PATIENT; IN VITRO STUDY; IN VIVO STUDY; LIMIT OF QUANTITATION; NEXT GENERATION SEQUENCING; NONHUMAN; PATHOGENESIS; PENICILLIUM CHRYSOGENUM; POLYMERASE CHAIN REACTION; PRICK TEST; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; TH17 CELL; TH2 CELL; ANIMAL; FUNGUS; IMMUNOLOGY; MICROBIOLOGY;

ANIMALS; ASTHMA; FUNGI; HUMANS; IMMUNOGLOBULIN E;

EID: 85003485951     PISSN: 15297322     EISSN: 15346315     Source Type: Journal    
DOI: 10.1007/s11882-016-0667-9     Document Type: Review

References (89)

1. Bloom B, Cohen RA, Freeman G. Summary health statistics for U.S. children: National Health Interview Survey, 2008. Vital and health statistics Series 10, Data from the National Health Survey. 2009(244):1–81.
2. Pleis JR, Lucas JW, Ward BW. Summary health statistics for U.S. adults: National Health Interview Survey, 2008. Vital and health statistics Series 10, Data from the National Health Survey. 2009(242):1–157.
3. McKinley L, Alcorn JF, Peterson A, Dupont RB, Kapadia S, Logar A, et al. TH17 cells mediate steroid-resistant airway inflammation and airway hyperresponsiveness in mice. J Immunol. 2008;181(6):4089–97.
4. Chesne J, Braza F, Mahay G, Brouard S, Aronica M, Magnan A. IL-17 in severe asthma. Where do we stand? Am J Respir Crit Care Med. 2014;190(10):1094–101. doi:10.1164/rccm.201405-0859PP.
5. Al-Ramli W, Prefontaine D, Chouiali F, Martin JG, Olivenstein R, Lemiere C, et al. T(H)17-associated cytokines (IL-17A and IL-17F) in severe asthma. J Allergy Clin Immunol. 2009;123(5):1185–7. doi:10.1016/j.jaci.2009.02.024.
6. Agache I, Ciobanu C, Agache C, Anghel M. Increased serum IL-17 is an independent risk factor for severe asthma. Respir Med. 2010;104(8):1131–7. doi:10.1016/j.rmed.2010.02.018.
7. Chien JW, Lin CY, Yang KD, Lin CH, Kao JK, Tsai YG. Increased IL-17A secreting CD4+ T cells, serum IL-17 levels and exhaled nitric oxide are correlated with childhood asthma severity. Clin Exp Allergy: J Br Soc Allergy Clin Immunol. 2013;43(9):1018–26. doi:10.1111/cea.12119.
8. Alyasin S, Karimi MH, Amin R, Babaei M, Darougar S. Interleukin-17 gene expression and serum levels in children with severe asthma. Iran J Immunol: IJI. 2013;10(3):177–85.
9. Dennehy KM, Willment JA, Williams DL, Brown GD. Reciprocal regulation of IL-23 and IL-12 following co-activation of Dectin-1 and TLR signaling pathways. Eur J Immunol. 2009;39(5):1379–86. doi:10.1002/eji.200838543.
10. Fuller GL, Williams JA, Tomlinson MG, Eble JA, Hanna SL, Pohlmann S, et al. The C-type lectin receptors CLEC-2 and Dectin-1, but not DC-SIGN, signal via a novel YXXL-dependent signaling cascade. J Biol Chem. 2007;282(17):12397–409. doi:10.1074/jbc.M609558200.
11. Tassi I, Cella M, Castro I, Gilfillan S, Khan WN, Colonna M. Requirement of phospholipase C-gamma2 (PLCgamma2) for Dectin-1-induced antigen presentation and induction of TH1/TH17 polarization. Eur J Immunol. 2009;39(5):1369–78. doi:10.1002/eji.200839313.
12. •• Zhang Z, Biagini Myers JM, Brandt EB, Ryan PH, Lindsey M, Mintz-Cole RA, et al. Beta-glucan exacerbates allergic asthma independent of fungal sensitization and promotes steroid-resistant TH2/TH17 responses. J Allergy Clin Immunol. 2016. doi:10.1016/j.jaci.2016.02.031. This paper integrated epidemiologic and experimental asthma models to explore the effect of fungal exposure on asthma development and severity. Fungal exposure enhances allergen-driven TH2 responses, promoting severe allergic asthma. This effect is independent of fungal sensitization and can be reconstituted with beta-glucan and abrogated by neutralization of IL-17A. Similarly, in children with asthma, fungal exposure was associated with increased serum IL-17A levels and asthma severity. This paper demonstrated that fungi are potent immunomodulators and have powerful effects on asthma independent of their potential to act as antigens.
13. Sahakian NM, Park JH, Cox-Ganser JM. Dampness and mold in the indoor environment: implications for asthma. Immunol Allergy Clin North Am. 2008;28(3):485–505. doi:10.1016/j.iac.2008.03.009.
14. Cho SH, Reponen T, LeMasters G, Levin L, Huang J, Meklin T, et al. Mold damage in homes and wheezing in infants. AnnAllergy, Asthma Immunol: Off Publ Am Coll Allergy, Asthma, Immunol. 2006;97(4):539–45. doi:10.1016/S1081-1206(10)60947-7.
15. • Iossifova YY, Reponen T, Ryan PH, Levin L, Bernstein DI, Lockey JE, et al. Mold exposure during infancy as a predictor of potential asthma development. AnnAllergy, Asthma Immunol: Off Publ Am Coll Allergy, Asthma, Immunol. 2009;102(2):131–7. doi:10.1016/S1081-1206(10)60243-8. In this study, visible mold was evaluated by means of home inspection. (1–3)-Beta-D-glucan levels were measured in settled dust, and its association with the risk for asthma at later ages was assessed. The study indicated that the presence of high visible mold and mother’s smoking during infancy were the strongest risk factors for a positive API at the age of 3 years, suggesting an increased risk of asthma. High (1–3)-beta-D-glucan exposure seems to have an opposite effect on API than does visible mold.
16. •• Reponen T, Vesper S, Levin L, Johansson E, Ryan P, Burkle J, et al. High environmental relative moldiness index during infancy as a predictor of asthma at 7 years of age. AnnAllergy, Asthma Immunol: Off Publ Am Coll Allergy, Asthma, Immunol. 2011;107(2):120–6. doi:10.1016/j.anai.2011.04.018. This study followed up a high-risk birth cohort from infancy to 7 years of age. Mold was assessed by a DNA-based analysis for the 36 molds that make up the Environmental Relative Moldiness Index at the ages of 1 and 7 years. The study indicated that early exposure to molds as measured by ERMI at 1 year of age, but not 7 years of age, significantly increased the risk for asthma at 7 years of age.
17. Levetin E. An atlas of fungal spores. J Allergy Clin Immunol. 2004;113(2):366–8. doi:10.1016/j.jaci.2003.09.049.
18. Walker GM WN. Introduction to fungal physiology. In: Kavanagh K, editor. Fungi: Biology and applications. John Wiley and Sons, Ltd.; 2005. 1–34.
19. Erwig LP, Gow NA. Interactions of fungal pathogens with phagocytes. Nat Rev Microbiol. 2016;14(3):163–76. doi:10.1038/nrmicro.2015.21.
20. Levitz SM. Innate recognition of fungal cell walls. PLoS Pathog. 2010;6(4), e1000758. doi:10.1371/journal.ppat.1000758.
21. Tischer C, Chen CM, Heinrich J. Association between domestic mould and mould components, and asthma and allergy in children: a systematic review. Eur Respir J. 2011;38(4):812–24. doi:10.1183/09031936.00184010.
22. Mintz-Cole RA, Brandt EB, Bass SA, Gibson AM, Reponen T, Khurana Hershey GK. Surface availability of beta-glucans is critical determinant of host immune response to Cladosporium cladosporioides. J Allergy Clin Immunol. 2013;132(1):159–69. doi:10.1016/j.jaci.2013.01.003.
23. Aimanianda V, Bayry J, Bozza S, Kniemeyer O, Perruccio K, Elluru SR, et al. Surface hydrophobin prevents immune recognition of airborne fungal spores. Nature. 2009;460(7259):1117–21. doi:10.1038/nature08264.
24. Douwes J. (1–3)-Beta-D-glucans and respiratory health: a review of the scientific evidence. Indoor Air. 2005;15(3):160–9. doi:10.1111/j.1600-0668.2005.00333.x.
25. Gow NA, Netea MG, Munro CA, Ferwerda G, Bates S, Mora-Montes HM, et al. Immune recognition of Candida albicans beta-glucan by dectin-1. J Infect Dis. 2007;196(10):1565–71. doi:10.1086/523110.
26. Gantner BN, Simmons RM, Underhill DM. Dectin-1 mediates macrophage recognition of Candida albicans yeast but not filaments. EMBO J. 2005;24(6):1277–86. doi:10.1038/sj.emboj.7600594.
27. Yang H, Tong J, Lee CW, Ha S, Eom SH, Im YJ. Structural mechanism of ergosterol regulation by fungal sterol transcription factor Upc2. Nat Commun. 2015;6:6129. doi:10.1038/ncomms7129.
28. Yike I. Fungal proteases and their pathophysiological effects. Mycopathologia. 2011;171(5):299–323. doi:10.1007/s11046-010-9386-2.
29. H. A. Inhalation exposure and toxic effects of mycotoxins. In: Li D-W, editor. Biology of Microfungi, Fungal Biology. Switzerland: Springer International Publishing; 2016.
30. Reponen T, Seo SC, Grimsley F, Lee T, Crawford C, Grinshpun SA. Fungal fragments in moldy houses: a field study in homes in New Orleans and Southern Ohio. Atmos Environ. 2007;41(37):8140–9. doi:10.1016/j.atmosenv.2007.06.027.
31. Rylander R. Fungi in homes—how do we measure? Indoor Air. 2014;24(2):221–2. doi:10.1111/ina.12075.
32. Seo S, Choung JT, Chen BT, Lindsley WG, Kim KY. The level of submicron fungal fragments in homes with asthmatic children. Environ Res. 2014;131:71–6. doi:10.1016/j.envres.2014.02.015.
33. Mendell MJ, Mirer AG, Cheung K, Tong M, Douwes J. Respiratory and allergic health effects of dampness, mold, and dampness-related agents: a review of the epidemiologic evidence. Environ Health Perspect. 2011;119(6):748–56. doi:10.1289/ehp.1002410.
34. Casas L, Tischer C, Taubel M. Pediatric asthma and the indoor microbial environment. Curr Environ Health Rep. 2016;3(3):238–49. doi:10.1007/s40572-016-0095-y.
35. Vishwanath V, Sulyok M, Labuda R, Bicker W, Krska R. Simultaneous determination of 186 fungal and bacterial metabolites in indoor matrices by liquid chromatography/tandem mass spectrometry. Anal Bioanal Chem. 2009;395(5):1355–72. doi:10.1007/s00216-009-2995-2.
36. Vesper S, Wymer L. The relationship between environmental relative moldiness index values and asthma. Int J Hyg Environ Health. 2016;219(3):233–8. doi:10.1016/j.ijheh.2016.01.006.
37. Choi H, Byrne S, Larsen LS, Sigsgaard T, Thorne PS, Larsson L, et al. Residential culturable fungi, (1–3, 1–6)-beta-d-glucan, and ergosterol concentrations in dust are not associated with asthma, rhinitis, or eczema diagnoses in children. Indoor Air. 2014;24(2):158–70. doi:10.1111/ina.12068.
38. Karvonen AM, Hyvarinen A, Rintala H, Korppi M, Taubel M, Doekes G, et al. Quantity and diversity of environmental microbial exposure and development of asthma: a birth cohort study. Allergy. 2014;69(8):1092–101. doi:10.1111/all.12439.
39. Mensah-Attipoe J, Reponen T, Veijalainen AM, Rintala H, Taubel M, Rantakokko P, et al. Comparison of methods for assessing temporal variation of growth of fungi on building materials. Microbiology. 2016. doi:10.1099/mic.0.000372.
40. Reponen T, Singh U, Schaffer C, Vesper S, Johansson E, Adhikari A, et al. Visually observed mold and moldy odor versus quantitatively measured microbial exposure in homes. Sci Total Environ. 2010;408(22):5565–74. doi:10.1016/j.scitotenv.2010.07.090.
41. Sivasubramani SK, Niemeier RT, Reponen T, Grinshpun SA. Assessment of the aerosolization potential for fungal spores in moldy homes. Indoor Air. 2004;14(6):405–12. doi:10.1111/j.1600-0668.2004.00262.x.
42. Lee T, Grinshpun SA, Martuzevicius D, Adhikari A, Crawford CM, Reponen T. Culturability and concentration of indoor and outdoor airborne fungi in six single-family homes. Atmos Environ. 2006;40(16):2902–10. doi:10.1016/j.atmosenv.2006.01.011.
43. Iossifova Y, Reponen T, Sucharew H, Succop P, Vesper S. Use of (1–3)-beta-d-glucan concentrations in dust as a surrogate method for estimating specific fungal exposures. Indoor Air. 2008;18(3):225–32. doi:10.1111/j.1600-0668.2008.00526.x.
44. Chew GL, Rogers C, Burge HA, Muilenberg ML, Gold DR. Dustborne and airborne fungal propagules represent a different spectrum of fungi with differing relations to home characteristics. Allergy. 2003;58(1):13–20.
45. Reponen T, Willeke K, Grinshpun S, Nevalainen A. Biological particle sampling. In: Kulkarni P, Baron, P., Willeke, K., editor. Aerosol Measurement, Principles, Techniques, and Applications, 3rd edition. John Wiley & Johns, Inc.; 2011. 549–70.
46. Macher J, Douwes J, Prezant B, Reponen T. Bioaerosols. In: Ruzer LaHNM, editor. Aerosol Handbook. CRC press; 2013. p. 285–343.
47. WHO Guidelines for Indoor Air Quality: Dampness and Mould. WHO Guidelines Approved by the Guidelines Review Committee. Geneva. 2009.
48. Kanchongkittiphon W, Mendell MJ, Gaffin JM, Wang G, Phipatanakul W. Indoor environmental exposures and exacerbation of asthma: an update to the 2000 review by the Institute of Medicine. Environ Health Perspect. 2015;123(1):6–20. doi:10.1289/ehp.1307922.
49. Rylander R, Norrhall M, Engdahl U, Tunsater A, Holt PG. Airways inflammation, atopy, and (1–3)-beta-D-glucan exposures in two schools. Am J Respir Crit Care Med. 1998;158(5 Pt 1):1685–7. doi:10.1164/ajrccm.158.5.9712139.
50. Ronmark E, Jonsson E, Platts-Mills T, Lundback B. Different pattern of risk factors for atopic and nonatopic asthma among children—report from the obstructive lung disease in Northern Sweden Study. Allergy. 1999;54(9):926–35.
51. Schram-Bijkerk D, Doekes G, Douwes J, Boeve M, Riedler J, Ublagger E, et al. Bacterial and fungal agents in house dust and wheeze in children: the PARSIFAL study. Clin Exp Allergy: J Br Soc Allergy Clin Immunol. 2005;35(10):1272–8. doi:10.1111/j.1365-2222.2005.02339.x.
52. Bernstein JA, Bobbitt RC, Levin L, Floyd R, Crandall MS, Shalwitz RA, et al. Health effects of ultraviolet irradiation in asthmatic children’s homes. J Asthma: Off J Assoc Care Asthma. 2006;43(4):255–62. doi:10.1080/02770900600616887.
53. Inal A, Karakoc GB, Altintas DU, Guvenmez HK, Aka Y, Gelisken R, et al. Effect of indoor mold concentrations on daily symptom severity of children with asthma and/or rhinitis monosensitized to molds. J Asthma: Off J Assoc Care Asthma. 2007;44(7):543–6. doi:10.1080/02770900701496130.
54. Pongracic JA, O’Connor GT, Muilenberg ML, Vaughn B, Gold DR, Kattan M, et al. Differential effects of outdoor versus indoor fungal spores on asthma morbidity in inner-city children. J Allergy Clin Immunol. 2010;125(3):593–9. doi:10.1016/j.jaci.2009.10.036.
55. Gent JF, Kezik JM, Hill ME, Tsai E, Li DW, Leaderer BP. Household mold and dust allergens: exposure, sensitization and childhood asthma morbidity. Environ Res. 2012;118:86–93. doi:10.1016/j.envres.2012.07.005.
56. Maheswaran D, Zeng Y, Chan-Yeung M, Scott J, Osornio-Vargas A, Becker AB, et al. Exposure to Beta-(1,3)-D-glucan in house dust at age 7–10 is associated with airway hyperresponsiveness and atopic asthma by age 11–14. PLoS One. 2014;9(6), e98878. doi:10.1371/journal.pone.0098878.
57. Sharpe RA, Bearman N, Thornton CR, Husk K, Osborne NJ. Indoor fungal diversity and asthma: a meta-analysis and systematic review of risk factors. J Allergy Clin Immunol. 2015;135(1):110–22. doi:10.1016/j.jaci.2014.07.002.
58. • Dannemiller KC, Gent JF, Leaderer BP, Peccia J. Indoor microbial communities: influence on asthma severity in atopic and nonatopic children. J Allergy Clin Immunol. 2016;138(1):76–83 e1. doi:10.1016/j.jaci.2015.11.027. The associations between exposures to household microbes and childhood asthma severity were assessed and stratified by atopic status. The study indicated that asthma severity in atopic children was associated with fungal community composition.
59. Iossifova YY, Reponen T, Bernstein DI, Levin L, Kalra H, Campo P, et al. House dust (1–3)-beta-D-glucan and wheezing in infants. Allergy. 2007;62(5):504–13. doi:10.1111/j.1398-9995.2007.01340.x.
60. Sharpe RA, Thornton CR, Tyrrell J, Nikolaou V, Osborne NJ. Variable risk of atopic disease due to indoor fungal exposure in NHANES 2005–2006. Clin Exp Allergy: J Br Soc Allergy Clin Immunol. 2015;45(10):1566–78. doi:10.1111/cea.12549.
61. Lambrecht BN, Hammad H. The immunology of asthma. Nat Immunol. 2015;16(1):45–56. doi:10.1038/ni.3049.
62. Roy RM, Klein BS. Fungal glycan interactions with epithelial cells in allergic airway disease. Curr Opin Microbiol. 2013;16(4):404–8. doi:10.1016/j.mib.2013.03.004.
63. Hardison SE, Brown GD. C-type lectin receptors orchestrate antifungal immunity. Nat Immunol. 2012;13(9):817–22. doi:10.1038/ni.2369.
64. Kataoka K, Muta T, Yamazaki S, Takeshige K. Activation of macrophages by linear (1right-arrow3)-beta-D-glucans. Impliations for the recognition of fungi by innate immunity. J Biol Chem. 2002;277(39):36825–31. doi:10.1074/jbc.M206756200.
65. Rand TG, Robbins C, Rajaraman D, Sun M, Miller JD. Induction of Dectin-1 and asthma-associated signal transduction pathways in RAW 264.7 cells by a triple-helical (1, 3)-beta-D glucan, curdlan. Arch Toxicol. 2013;87(10):1841–50. doi:10.1007/s00204-013-1042-4.
66. Carmona EM, Lamont JD, Xue A, Wylam M, Limper AH. Pneumocystis cell wall beta-glucan stimulates calcium-dependent signaling of IL-8 secretion by human airway epithelial cells. Respir Res. 2010;11:95. doi:10.1186/1465-9921-11-95.
67. Nathan AT, Peterson EA, Chakir J, Wills-Karp M. Innate immune responses of airway epithelium to house dust mite are mediated through beta-glucan-dependent pathways. J Allergy Clin Immunol. 2009;123(3):612–8. doi:10.1016/j.jaci.2008.12.006.
68. Neveu WA, Bernardo E, Allard JL, Nagaleekar V, Wargo MJ, Davis RJ, et al. Fungal allergen beta-glucans trigger p38 mitogen-activated protein kinase-mediated IL-6 translation in lung epithelial cells. Am J Respir Cell Mol Biol. 2011;45(6):1133–41. doi:10.1165/rcmb.2011-0054OC.
69. Ryu JH, Yoo JY, Kim MJ, Hwang SG, Ahn KC, Ryu JC, et al. Distinct TLR-mediated pathways regulate house dust mite-induced allergic disease in the upper and lower airways. J Allergy Clin Immunol. 2013;131(2):549–61. doi:10.1016/j.jaci.2012.07.050.
70. Rand TG, Sun M, Gilyan A, Downey J, Miller JD. Dectin-1 and inflammation-associated gene transcription and expression in mouse lungs by a toxic (1,3)-beta-D glucan. Arch Toxicol. 2010;84(3):205–20. doi:10.1007/s00204-009-0481-4.
71. Inoue K, Koike E, Yanagisawa R, Adachi Y, Ishibashi K, Ohno N, et al. Pulmonary exposure to soluble cell wall beta-(1, 3)-glucan of aspergillus induces proinflammatory response in mice. Int J Immunopathol Pharmacol. 2009;22(2):287–97.
72. Liu H, Zheng M, Qiao J, Dang Y, Zhang P, Jin X. Role of prostaglandin D2/CRTH2 pathway on asthma exacerbation induced by Aspergillus fumigatus. Immunology. 2014;142(1):78–88. doi:10.1111/imm.12234.
73. Fakih D, Pilecki B, Schlosser A, Jepsen CS, Thomsen LK, Ormhoj M, et al. Protective effects of surfactant protein D treatment in 1,3-beta-glucan-modulated allergic inflammation. Am J Physiol Lung Cell Mol Physiol. 2015;309(11):L1333–43. doi:10.1152/ajplung.00090.2015.
74. Irvin C, Zafar I, Good J, Rollins D, Christianson C, Gorska MM, et al. Increased frequency of dual-positive TH2/TH17 cells in bronchoalveolar lavage fluid characterizes a population of patients with severe asthma. J Allergy Clin Immunol. 2014;134(5):1175–86. doi:10.1016/j.jaci.2014.05.038. e7.
75. Wang YH, Voo KS, Liu B, Chen CY, Uygungil B, Spoede W, et al. A novel subset of CD4(+) T(H)2 memory/effector cells that produce inflammatory IL-17 cytokine and promote the exacerbation of chronic allergic asthma. J Exp Med. 2010;207(11):2479–91. doi:10.1084/jem.20101376.
76. Burg AR, Quigley L, Jones AV, O’Connor GM, Boelte K, McVicar DW, et al. Orally administered beta-glucan attenuates the Th2 response in a model of airway hypersensitivity. Springer Plus. 2016;5(1):815. doi:10.1186/s40064-016-2501-1.
77. Kawashima S, Hirose K, Iwata A, Takahashi K, Ohkubo A, Tamachi T, et al. beta-glucan curdlan induces IL-10-producing CD4+ T cells and inhibits allergic airway inflammation. J Immunol. 2012;189(12):5713–21. doi:10.4049/jimmunol.1201521.
78. Ku SK, Kim JW, Cho HR, Kim KY, Min YH, Park JH, et al. Effect of beta-glucan originated from Aureobasidium pullulans on asthma induced by ovalbumin in mouse. Arch Pharm Res. 2012;35(6):1073–81. doi:10.1007/s12272-012-0615-8.
79. Lin JY, Chen JS, Chen PC, Chung MH, Liu CY, Miaw SC, et al. Concurrent exposure to a Dectin-1 agonist suppresses the Th2 response to epicutaneously introduced antigen in mice. J Biomed Sci. 2013;20:1. doi:10.1186/1423-0127-20-1.
80. Brinchmann BC, Bayat M, Brogger T, Muttuvelu DV, Tjonneland A, Sigsgaard T. A possible role of chitin in the pathogenesis of asthma and allergy. Ann Agric Environ Med: AAEM. 2011;18(1):7–12.
81. Mack I, Hector A, Ballbach M, Kohlhaufl J, Fuchs KJ, Weber A, et al. The role of chitin, chitinases, and chitinase-like proteins in pediatric lung diseases. Mol Cell Pedia. 2015;2(1):3. doi:10.1186/s40348-015-0014-6.
82. Reese TA, Liang HE, Tager AM, Luster AD, Van Rooijen N, Voehringer D, et al. Chitin induces accumulation in tissue of innate immune cells associated with allergy. Nature. 2007;447(7140):92–6. doi:10.1038/nature05746.
83. Shibata Y, Foster LA, Metzger WJ, Myrvik QN. Alveolar macrophage priming by intravenous administration of chitin particles, polymers of N-acetyl-D-glucosamine, in mice. Infect Immun. 1997;65(5):1734–41.
84. Van Dyken SJ, Garcia D, Porter P, Huang X, Quinlan PJ, Blanc PD, et al. Fungal chitin from asthma-associated home environments induces eosinophilic lung infiltration. J Immunol. 2011;187(5):2261–7. doi:10.4049/jimmunol.1100972.
85. • Van Dyken SJ, Mohapatra A, Nussbaum JC, Molofsky AB, Thornton EE, Ziegler SF, et al. Chitin activates parallel immune modules that direct distinct inflammatory responses via innate lymphoid type 2 and gammadelta T cells. Immunity. 2014;40(3):414–24. doi:10.1016/j.immuni.2014.02.003. This paper showed that inhaled chitin induced expression of three epithelial cytokines, IL-25, IL-33, and TSLP, which nonredundantly activated resident ILC2s to express IL-5 and IL-13 necessary for accumulation of eosinophils and alternatively activated macrophages. Thus, chitin elicited patterns of innate cytokines that targeted distinct populations of resident lymphoid cells, revealing divergent but interacting pathways underlying the tissue accumulation of specific types of inflammatory myeloid cells.
86. Khosravi AR, Erle DJ. Chitin-induced airway epithelial cell innate immune responses are inhibited by carvacrol/thymol. PLoS One. 2016;11(7), e0159459. doi:10.1371/journal.pone.0159459.
87. O’Dea EM, Amarsaikhan N, Li H, Downey J, Steele E, Van Dyken SJ, et al. Eosinophils are recruited in response to chitin exposure and enhance Th2-mediated immune pathology in Aspergillus fumigatus infection. Infect Immun. 2014;82(8):3199–205. doi:10.1128/IAI.01990-14.
88. • Balenga NA, Klichinsky M, Xie Z, Chan EC, Zhao M, Jude J, et al. A fungal protease allergen provokes airway hyper-responsiveness in asthma. Nat Commun. 2015;6:6763. doi:10.1038/ncomms7763. This paper showed that a major Af allergen, Asp f13, which is a serine protease, promotes airway hyper-responsiveness by infiltrating the bronchial submucosa and disrupting airway smooth muscle cell-extracellular matrix (ECM) interactions. Alp 1-mediated ECM degradation evokes pathophysiological RhoA-dependent Ca(2+) sensitivity and bronchoconstriction. These findings support a pathogenic mechanism in asthma and other lung diseases associated with epithelial barrier impairment, whereby ASM cells respond directly to inhaled environmental allergens to generate airway hyper-responsiveness.
89. • Millien VO, Lu W, Shaw J, Yuan X, Mak G, Roberts L, et al. Cleavage of fibrinogen by proteinases elicits allergic responses through Toll-like receptor 4. Science. 2013;341(6147):792–6. doi:10.1126/science.1240342. This paper demonstrated that TLR4 is activated by airway proteinase activity to initiate both allergic airway disease and antifungal immunity. These outcomes were induced by proteinase cleavage of the clotting protein fibrinogen, yielding fibrinogen cleavage products that acted as TLR4 ligands on airway epithelial cells and macrophages.