PMID- 23711857 OWN - NLM STAT- MEDLINE DCOM- 20130724 LR - 20211021 IS - 1423-0097 (Electronic) IS - 1018-2438 (Print) IS - 1018-2438 (Linking) VI - 161 Suppl 2 IP - 0 2 DP - 2013 TI - Alternaria inhibits double-stranded RNA-induced cytokine production through Toll-like receptor 3. PG - 75-83 LID - 10.1159/000350365 [doi] AB - BACKGROUND: Fungi may be involved in asthma and chronic rhinosinusitis (CRS). Peripheral blood mononuclear cells from CRS patients produce interleukin (IL)-5, IL-13 and interferon (IFN)-gamma in the presence of Alternaria. In addition, Alternaria produces potent Th2-like adjuvant effects in the airway. Therefore, we hypothesized that Alternaria may inhibit Th1-type defense mechanisms against virus infection. METHODS: Dendritic cells (DCs) were generated from mouse bone marrow. The functional responses were assessed by expression of cell surface molecules by FACS (MHC class II, CD40, CD80, CD86 and OX40L). Production of IL-6, chemokine CXCL10 (IP-10), chemokine CXCL11 (I-TAC) and IFN-beta was measured by ELISA. Toll-like receptor 3 (TLR3) mRNA and protein expression was detected by quantitative real-time PCR and Western blot. RESULTS: Alternaria and polyinosinic-polycytidylic acid (poly I:C) enhanced cell surface expression of MHC class II, CD40, CD80, CD86 and OX40L, and IL-6 production in a concentration-dependent manner. However, Alternaria significantly inhibited production of IP-10, I-TAC and IFN-beta, induced by viral double-stranded RNA (dsRNA) mimic poly I:C. TLR3 mRNA expression and protein production by poly I:C were significantly inhibited by Alternaria. These reactions are likely caused by heat-stable factor(s) in Alternaria extract with >100 kDa molecular mass. CONCLUSION: These findings suggest that the fungus Alternaria may inhibit production of IFN-beta and other cytokines by DCs by suppressing TLR3 expression. These results indicate that Alternaria may inhibit host innate immunity against virus infection. CI - Copyright (c) 2013 S. Karger AG, Basel. FAU - Wada, Kota AU - Wada K AD - Department of Otorhinolaryngology, Toho University, Tokyo, Japan. wadakota@med.toho-u.ac.jp FAU - Kobayashi, Takao AU - Kobayashi T FAU - Matsuwaki, Yoshinori AU - Matsuwaki Y FAU - Moriyama, Hiroshi AU - Moriyama H FAU - Kita, Hirohito AU - Kita H LA - eng GR - R01 AI071106/AI/NIAID NIH HHS/United States GR - R37 AI071106/AI/NIAID NIH HHS/United States GR - R01 AI049235/AI/NIAID NIH HHS/United States GR - AI49235/AI/NIAID NIH HHS/United States GR - AI71106/AI/NIAID NIH HHS/United States GR - R56 AI049235/AI/NIAID NIH HHS/United States GR - R01 HL110539/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20130529 PL - Switzerland TA - Int Arch Allergy Immunol JT - International archives of allergy and immunology JID - 9211652 RN - 0 (Chemokine CXCL10) RN - 0 (Chemokine CXCL11) RN - 0 (Cxcl10 protein, mouse) RN - 0 (Cxcl11 protein, mouse) RN - 0 (Cytokines) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Interleukin-6) RN - 0 (RNA, Double-Stranded) RN - 0 (Toll-Like Receptor 3) RN - O84C90HH2L (Poly I-C) SB - IM MH - Alternaria/chemistry/*immunology MH - Animals MH - Chemokine CXCL10/biosynthesis MH - Chemokine CXCL11/biosynthesis MH - Cytokines/*biosynthesis MH - Dendritic Cells/immunology/metabolism MH - Female MH - Gene Expression Regulation/drug effects MH - Histocompatibility Antigens Class II/immunology MH - Interleukin-6/biosynthesis MH - Mice MH - Poly I-C/immunology/pharmacology MH - RNA, Double-Stranded/*immunology MH - Toll-Like Receptor 3/genetics/*metabolism PMC - PMC3904297 MID - NIHMS546684 COIS- Disclosures The authors have no financial conflict of interest. EDAT- 2013/06/05 06:00 MHDA- 2013/07/25 06:00 PMCR- 2014/05/29 CRDT- 2013/05/29 06:00 PHST- 2013/05/29 06:00 [entrez] PHST- 2013/06/05 06:00 [pubmed] PHST- 2013/07/25 06:00 [medline] PHST- 2014/05/29 00:00 [pmc-release] AID - 000350365 [pii] AID - 10.1159/000350365 [doi] PST - ppublish SO - Int Arch Allergy Immunol. 2013;161 Suppl 2(0 2):75-83. doi: 10.1159/000350365. Epub 2013 May 29.