title: Th2 allergic immune response to inhaled fungal antigens is modulated by TLR-4-independent bacterial products.
abstract: Allergic airway disease is characterized by eosinophilic inflammation, mucus hypersecretion and increased airway resistance. Fungal antigens are ubiquitous within the environment and are well known triggers of allergic disease. Bacterial products are also frequently encountered within the environment and may alter the immune response to certain antigens. The consequence of simultaneous exposure to bacterial and fungal products on the lung adaptive immune response has not been explored. Here, we show that oropharyngeal aspiration of fungal lysates (Candida albicans, Aspergillus fumigatus) promotes airway eosinophilia, secretion of Th2 cytokines and mucus cell metaplasia. In contrast, oropharyngeal exposure to bacterial lysates (Pseudomonas aeruginosa) promotes airway inflammation characterized by neutrophils, Th1 cytokine secretion and no mucus production. More importantly, administration of bacterial lysates together with fungal lysates deviates the adaptive immune response to a Th1 type associated with neutrophilia and diminished mucus production. The immunomodulatory effect that bacterial lysates have on the response to fungi is TLR4 independent but MyD88 dependent. Thus, different types of microbial products within the airway can alter the host's adaptive immune response and potentially impact the development of allergic airway disease to environmental fungal antigens.
authors.affiliation: Department of Medicine, Division of Pulmonary Disease and Critical Care, Vermont Lung Center, University of Vermont, Burlington, VT, USA.
authors.forename: Jenna B
authors.initials: JB
authors.lastname: Allard
authors.forename: Lisa
authors.initials: L
authors.lastname: Rinaldi
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Wargo
authors.forename: Gilman
authors.initials: G
authors.lastname: Allen
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uematsu
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Poynter
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Hogan
authors.forename: Mercedes
authors.initials: M
authors.lastname: Rincon
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Whittaker
mesh_terms: D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology* / Q000378:metabolism; D001232:Aspergillus fumigatus / Q000276:immunology; D001419:Bacteria / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology; D002457:Cell Extracts / Q000276:immunology* / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004804:Eosinophils / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D006967:Hypersensitivity / Q000276:immunology* / Q000382:microbiology; D007155:Immunologic Factors / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D008679:Metaplasia / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009093:Mucus / Q000276:immunology / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051197:Toll-Like Receptor 4 / Q000276:immunology; D000095983:Bacterial Lysates
chemical_list: D000946:Antigens, Fungal; D002457:Cell Extracts; D016207:Cytokines; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D051197:Toll-Like Receptor 4; C030259:Broncho-Vaxom; D000095983:Bacterial Lysates; C507780:Myd88 protein, mouse; C493487:Tlr4 protein, mouse