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Activation of mast cells by double-stranded RNA: evidence for activation through Toll-like receptor 3

Marianna Kulka1, Lena Alexopoulou, Richard A Flavell

  • 1Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1881, USA.

The Journal of Allergy and Clinical Immunology
|July 9, 2004
PubMed
Abstract

Insights

Mast cells (MCs) produce type I interferons (IFNs) in response to viral infections and double-stranded RNA. This suggests mast cells play a role in the innate immune system

Area of Science:

  • Immunology
  • Innate Immunity
  • Cell Biology

Background:

  • Mast cells (MCs) are known to be involved in bacterial innate immune responses.
  • The role of mast cells in responding to viral infections is less understood.

Purpose of the Study:

  • To investigate the ability of mast cells to produce cytokines, including type I interferons (IFNs), upon exposure to viruses and polyinosine-polycytidylic acid (polyI:C).
  • To characterize the specific receptors involved in mast cell activation by viral stimuli.

Main Methods:

  • Human and murine mast cells were stimulated with viruses and polyI:C.
  • Cytokine production, degranulation, and signaling pathways were analyzed.
  • Toll-like receptor (TLR) expression, particularly TLR-3, was examined using RT-PCR and Western blot.

Main Results:

  • Viruses and polyI:C induced the production of IFN-alpha and IFN-beta by mast cells.
  • IFN-alpha production was mediated by nuclear factor-kappaB, p38, and C-Jun NH2-terminal kinase signaling pathways.
  • TLR-3 expression was confirmed in mast cells, and antibodies to TLR-3 significantly reduced IFN-alpha production. TLR-3 knockout mice showed an ablated response to polyI:C.

Conclusions:

  • Mast cells produce type I IFNs in response to viral double-stranded RNA, primarily through interactions with TLR-3.
  • These findings indicate that mast cells contribute to the innate immune response against viral infections by producing type I IFNs.

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