Type I interferon (IFN), mainly produced by dendritic cells (DCs), is critical in the host defence against tick-transmitted pathogens. Here, we report that salivary cysteine protease inhibitor from the hard tick Ixodes scapularis, sialostatin L2, affects IFN-β mediated immune reactions in mouse dendritic cells. Following IFN receptor ligation, the Janus activated kinases/signal transducer and activator of transcription (JAK/STAT) pathway is activated. We show that sialostatin L2 attenuates phosphorylation of STATs in spleen dendritic cells upon addition of recombinant IFN-β. LPS-stimulated dendritic cells release IFN-β which in turn leads to the induction of IFN-stimulated genes (ISG) through JAK/STAT pathway activation. The induction of two ISG, interferon regulatory factor 7 (IRF-7) and IP-10, was suppressed by sialostatin L2 in LPS-stimulated dendritic cells. Finally, the interference of sialostatin L2 with IFN action led to the enhanced replication of tick-borne encephalitis virus in DC. In summary, we present here that tick salivary cystatin negatively affects IFN-β responses which may consequently increase the pathogen load after transmission via tick saliva.
- MeSH
- Borrelia burgdorferi physiology MeSH
- Cystatins immunology MeSH
- Dendritic Cells immunology MeSH
- Phosphorylation MeSH
- Interferon-beta immunology MeSH
- Interferon Regulatory Factor-7 immunology MeSH
- Ixodes immunology microbiology MeSH
- Lipopolysaccharides immunology MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Receptors, Cytokine immunology MeSH
- Receptors, Interferon metabolism MeSH
- Salivary Cystatins immunology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Type I interferons (IFN-α and IFN-β) are crucial determinants of the host immune response and tick saliva modulates this response, thus facilitating the transmission of tickborne pathogens. The current study therefore examines the effect of Ixodes ricinus tick saliva on IFN-β signalling in murine dendritic cells using lipopolysaccharide (LPS) and Borrelia afzelii spirochaetes as inducers. Activated dendritic cells secret IFN that activates Signal Transducer and Activator of Transcription 1 (STAT-1). Our results show that Borrelia-induced activation of STAT-1 was suppressed by tick saliva. As the amount of secreted IFN-β was not influenced by tick saliva, the results indicated that saliva affected the interferon pathway at the IFN receptor or downstream of it. By using recombinant IFN-β, we show that tick saliva attenuates IFN-triggered STAT-1 activation. Tick saliva also inhibited LPS-induced IFN-β production suggesting that saliva interferes with the activation of the pathway that mediates IFN-β induction. Our data indicate that I. ricinus tick saliva may modulate the host immune response by attenuating the initial signal transduction pathway of type I IFN.
- MeSH
- Borrelia burgdorferi Group pathogenicity MeSH
- Dendritic Cells immunology MeSH
- Immunologic Factors immunology metabolism MeSH
- Interferon Type I antagonists & inhibitors immunology MeSH
- Ixodes immunology MeSH
- Cells, Cultured MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Saliva immunology metabolism MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH