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

Although mast cells (MCs) have been clearly implicated in innate immune responses involving bacteria, their ability to respond to viral infection is less clear. Given that MCs increase at sites of inflammation and are located at surfaces where exposure to invading viruses may occur, we explored the ability of MCs to produce cytokines including type I IFNs after exposure to viruses and to polyinosine-polycytidylic acid (polyI:C), a synthetic mimic of viral double-stranded RNA, and characterized the receptors involved, if any. Human peripheral blood-derived cultured MCs and 2 MC lines, Laboratory of Allergic Disease MC line and human MC line 1, were stimulated with viruses and polyI:C, and cytokine production, degranulation, and signaling pathway activation were examined. Because polyI:C is a ligand for Toll-like receptor (TLR)-3, human MCs were also analyzed for TLR expression. Viruses and polyI:C induced IFN-alpha and IFN-beta production. PolyI:C did not induce TNF, IL-1beta, IL-5, or GM-CSF production, in contrast with other TLR ligands (LPS, peptidoglycan, CpG-A, or flagellin). IFN-alpha production involved nuclear factor-kappaB, p38, and C-Jun NH2-terminal kinase and mitogen-activated protein kinase. RT-PCR and Western blot analysis confirmed expression of TLR-3 by all MCs. Human cultured MCs also expressed TLR-1, TLR-2, TLR-4, TLR-5, TLR-6, TLR-7 and TLR-9. Antibodies to TLR-3 significantly decreased IFN-alpha production. Bone marrow-derived MCs from TLR-3 knockout mice showed an ablated response to polyI:C. Murine and human MCs produce type I IFNs after exposure to double-stranded RNA and/or virus, the former via specific interactions with TLR-3. These data suggest that MCs contribute to innate immune responses to viral infection via the production of type I IFNs.

Kulka M ，Alexopoulou L ，Flavell RA ，Metcalfe DD ... -  《JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY》

Expression and function of Toll-like receptors in chicken heterophils.

Kogut MH ，Iqbal M ，He H ，Philbin V ，Kaiser P ，Smith A ... -  《DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY》

Synergistic induction of CXCL9 and CXCL11 by Toll-like receptor ligands and interferon-gamma in fibroblasts correlates with elevated levels of CXCR3 ligands in septic arthritis synovial fluids.

Proost P ，Verpoest S ，Van de Borne K ，Schutyser E ，Struyf S ，Put W ，Ronsse I ，Grillet B ，Opdenakker G ，Van Damme J ... -  《JOURNAL OF LEUKOCYTE BIOLOGY》

Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3.

Alexopoulou L ，Holt AC ，Medzhitov R ，Flavell RA ... -  《NATURE》

Various members of the Toll-like receptor family contribute to the innate immune response of human epidermal keratinocytes.

Köllisch G ，Kalali BN ，Voelcker V ，Wallich R ，Behrendt H ，Ring J ，Bauer S ，Jakob T ，Mempel M ，Ollert M ... -  《-》