PMID- 26641462 OWN - NLM STAT- MEDLINE DCOM- 20160506 LR - 20220316 IS - 1423-0097 (Electronic) IS - 1018-2438 (Linking) VI - 168 IP - 2 DP - 2015 TI - The Role of Toll-Like Receptors and Myeloid Differentiation Factor 88 in Bjerkandera adusta-Induced Lung Inflammation. PG - 96-106 LID - 10.1159/000441895 [doi] AB - 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-alpha, MCP-1, and macrophage inflammatory protein-1alpha 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. CI - (c) 2015 S. Karger AG, Basel. FAU - He, Miao AU - He M AD - Environment and Non-Communicable Disease Research Center, School of Public Health, China Medical University, Shenyang, China. FAU - Ichinose, Takamichi AU - Ichinose T FAU - Song, Yuan AU - Song Y FAU - Yoshida, Yasuhiro AU - Yoshida Y FAU - Kobayashi, Fumihisa AU - Kobayashi F FAU - Maki, Teruya AU - Maki T FAU - Yoshida, Seiichi AU - Yoshida S FAU - Takano, Hirohisa AU - Takano H FAU - Shibamoto, Takayuki AU - Shibamoto T FAU - Sun, Guifan AU - Sun G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151208 PL - Switzerland TA - Int Arch Allergy Immunol JT - International archives of allergy and immunology JID - 9211652 RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (Myd88 protein, mouse) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Toll-Like Receptors) RN - 0 (beta-Glucans) SB - IM MH - Animals MH - Bone Marrow Cells/cytology MH - Bronchoalveolar Lavage Fluid/cytology/immunology MH - Cell Count MH - Cells, Cultured MH - *Coriolaceae/metabolism MH - Cytokines/immunology MH - Lipopolysaccharides/metabolism MH - Lung/immunology/pathology MH - Macrophages/immunology MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Mycoses/*immunology/pathology MH - Myeloid Differentiation Factor 88/genetics/*immunology MH - Pneumonia/*immunology/pathology MH - Toll-Like Receptors/genetics/*immunology MH - beta-Glucans/metabolism EDAT- 2015/12/08 06:00 MHDA- 2016/05/07 06:00 CRDT- 2015/12/08 06:00 PHST- 2015/01/23 00:00 [received] PHST- 2015/10/19 00:00 [accepted] PHST- 2015/12/08 06:00 [entrez] PHST- 2015/12/08 06:00 [pubmed] PHST- 2016/05/07 06:00 [medline] AID - 000441895 [pii] AID - 10.1159/000441895 [doi] PST - ppublish SO - Int Arch Allergy Immunol. 2015;168(2):96-106. doi: 10.1159/000441895. Epub 2015 Dec 8.