title: The β-glucan receptor dectin-1 promotes lung immunopathology during fungal allergy via IL-22.
abstract: Sensitization to fungi, such as the mold Aspergillus fumigatus, is increasingly becoming linked with asthma severity. We have previously shown that lung responses generated via the β-glucan receptor Dectin-1 are required for lung defense during acute, invasive A. fumigatus infection. Unexpectedly, in an allergic model of chronic lung exposure to live A. fumigatus conidia, β-glucan recognition via Dectin-1 led to the induction of multiple proallergic (Muc5ac, Clca3, CCL17, CCL22, and IL-33) and proinflammatory (IL-1β and CXCL1) mediators that compromised lung function. Attenuated proallergic and proinflammatory responses in the absence of Dectin-1 were not associated with changes in Ido (IDO), Il12p35/Ebi3 (IL-35), IL-10, or TGF-β levels. Assessment of Th responses demonstrated that purified lung CD4(+) T cells produced IL-4, IL-13, IFN-γ, and IL-17A, but not IL-22, in a Dectin-1-dependent manner. In contrast, we observed robust, Dectin-1-dependent IL-22 production by unfractionated lung digest cells. Intriguingly, the absence of IL-22 alone mimicked the attenuated proallergic and proinflammatory responses observed in the absence of Dectin-1, suggesting that Dectin-1-mediated IL-22 production potentiated responses that led to decrements in lung function. To this end, neutralization of IL-22 improved lung function in normal mice. Collectively, these results indicate that the β-glucan receptor Dectin-1 contributes to lung inflammation and immunopathology associated with persistent fungal exposure via the production of IL-22.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Lilly
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Gessner
authors.forename: Chad W
authors.initials: CW
authors.lastname: Dunaway
authors.forename: Allison E
authors.initials: AE
authors.lastname: Metz
authors.forename: Lisa
authors.initials: L
authors.lastname: Schwiebert
authors.forename: Casey T
authors.initials: CT
authors.lastname: Weaver
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Brown
authors.forename: Chad
authors.initials: C
authors.lastname: Steele
mesh_terms: D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology*; D002478:Cells, Cultured; D002908:Chronic Disease; D004195:Disease Models, Animal; D005936:Glucans / Q000378:metabolism*; D007378:Interleukins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D037181:Lectins, C-Type / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000502:physiology*; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D000097043:Interleukin-22; D000099181:Dectin-1
chemical_list: D005936:Glucans; D007378:Interleukins; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D000097043:Interleukin-22; D000099181:Dectin-1; C045268:beta-glucan receptor