Alternaria inhibits double-stranded RNA-induced cytokine production through Toll-like receptor 3.

Kota Wada, Takao Kobayashi, Yoshinori Matsuwaki, Hiroshi Moriyama, Hirohito Kita

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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. 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. 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. 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.

Original languageEnglish (US)
Pages (from-to)75-83
Number of pages9
JournalInternational Archives of Allergy and Immunology
Volume161 Suppl 2
DOIs
StatePublished - 2013

Fingerprint

Toll-Like Receptor 3
Alternaria
Double-Stranded RNA
Cytokines
Interferons
Poly I-C
Virus Diseases
Dendritic Cells
Chemokine CXCL11
Interleukin-6
Fungi
Chemokine CXCL10
Poly C
Messenger RNA
Interleukin-13
Interleukin-5
Viral RNA
Innate Immunity
Real-Time Polymerase Chain Reaction
Blood Cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Alternaria inhibits double-stranded RNA-induced cytokine production through Toll-like receptor 3. / Wada, Kota; Kobayashi, Takao; Matsuwaki, Yoshinori; Moriyama, Hiroshi; Kita, Hirohito.

In: International Archives of Allergy and Immunology, Vol. 161 Suppl 2, 2013, p. 75-83.

Research output: Contribution to journalArticle

Wada, Kota ; Kobayashi, Takao ; Matsuwaki, Yoshinori ; Moriyama, Hiroshi ; Kita, Hirohito. / Alternaria inhibits double-stranded RNA-induced cytokine production through Toll-like receptor 3. In: International Archives of Allergy and Immunology. 2013 ; Vol. 161 Suppl 2. pp. 75-83.
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