title: The Role of Toll-Like Receptors and Myeloid Differentiation Factor 88 in Bjerkandera adusta-Induced Lung Inflammation.
abstract: BACKGROUND
  Recently, a cluster of patients with an intractable allergic fungal cough who were characterized by sensitization to Bjerkandera adusta was reported. In the present study, the role of Toll-like receptors and myeloid differentiation factor 88 (MyD88) in B. adusta-induced lung inflammation was investigated.
  
  
  METHODS
  Wild-type (WT), TLR2-/-,TLR4-/-, and MyD88-/- BALB/c mice were intratracheally challenged with B. adusta 4 times at 2-week intervals. Lung pathology, bronchoalveolar lavage fluid (BALF) cytological profiles, and inflammatory mediators in BALF were investigated. Bone marrow-derived macrophages (BMDM) from TLR2-/-,TLR4-/-, TLR2/4-/-, TLR7/9-/-,MyD88-/-, and WT C57BL/6J mice were stimulated with B. adusta for 12 h, and inflammatory mediators in the culture medium were measured.
  
  
  RESULTS
  B. adusta caused lung inflammation along with Th2 cytokine [interleukin (IL)-5 and IL-13] and eosinophil-related chemokine [eotaxin and monocyte chemotactic protein (MCP-3)] production, an increase in eosinophils in BALF, and eosinophil infiltration in the airways in WT and TLR4-/- mice. However, Th2 and eosinophil-related responses in TLR2-/- and MyD88-/- mice were low or undetectable. The induction of neutrophils and IL-6, IL-12, IL-17A, and MCP-1 in the BALF of MyD88-/- mice was attenuated compared to that in WT mice. The induction of IL-6, TNF-α, MCP-1, and macrophage inflammatory protein-1α was reduced or undetectable in B. adusta-stimulated BMDM from TLR7/9-/- and MyD88-/- mice compared to WT mice.
  
  
  CONCLUSIONS
  These results suggest that TLR2 and the adapter protein MyD88 may play an important role in the induction of eosinophils by B. adusta. However, TLR7/9-MyD88 might be important in the induction of neutrophils and the relevant inflammatory mediators, especially IL-17A.
authors.affiliation: Environment and Non-Communicable Disease Research Center, School of Public Health, China Medical University, Shenyang, China.
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.forename: Takamichi
authors.initials: T
authors.lastname: Ichinose
authors.forename: Yuan
authors.initials: Y
authors.lastname: Song
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Fumihisa
authors.initials: F
authors.lastname: Kobayashi
authors.forename: Teruya
authors.initials: T
authors.lastname: Maki
authors.forename: Seiichi
authors.initials: S
authors.lastname: Yoshida
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Takano
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shibamoto
authors.forename: Guifan
authors.initials: G
authors.lastname: Sun
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002452:Cell Count; D002478:Cells, Cultured; D055453:Coriolaceae / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D008070:Lipopolysaccharides / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009181:Mycoses / Q000276:immunology* / Q000473:pathology; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology*; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology*; D047071:beta-Glucans / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors; D047071:beta-Glucans