title: Alternaria inhibits double-stranded RNA-induced cytokine production through Toll-like receptor 3.
abstract: 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)-γ 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-β 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-β, 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.
  
  
  CONCLUSIONS
  These findings suggest that the fungus Alternaria may inhibit production of IFN-β and other cytokines by DCs by suppressing TLR3 expression. These results indicate that Alternaria may inhibit host innate immunity against virus infection.
authors.affiliation: Department of Otorhinolaryngology, Toho University, Tokyo, Japan. wadakota@med.toho-u.ac.jp
authors.forename: Kota
authors.initials: K
authors.lastname: Wada
authors.forename: Takao
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Matsuwaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Moriyama
authors.forename: Hirohito
authors.initials: H
authors.lastname: Kita
mesh_terms: D000528:Alternaria / Q000737:chemistry / Q000276:immunology*; D000818:Animals; D054357:Chemokine CXCL10 / Q000096:biosynthesis; D054371:Chemokine CXCL11 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000276:immunology*; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*
chemical_list: D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; C485433:Cxcl10 protein, mouse; C515203:Cxcl11 protein, mouse; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D015850:Interleukin-6; D012330:RNA, Double-Stranded; D051196:Toll-Like Receptor 3; D011070:Poly I-C