Tick salivary cystatin sialostatin L2 suppresses IFN responses in mouse dendritic cells.

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-ß 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-ß. LPS-stimulated dendritic cells release IFN-ß 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-ß responses which may consequently increase the pathogen load after transmission via tick saliva.

Effect of tick saliva on immune interactions between Borrelia afzelii and murine dendritic cells.

Interaction between mouse dendritic cells (DCs) and Borrelia afzelii spirochetes was monitored on three different levels: phagocytosis of spirochetes by DCs, production of cytokines by Borrelia-stimulated DCs and the ability of Borrelia-exposed DCs to activate specific CD4+ T lymphocytes. The effect of Ixodes ricinus tick saliva on each of these interactions was examined. Tick saliva was shown to decrease the number of phagocytosing DCs. The ability of Borrelia-exposed DCs to induce both proliferation and IL-2 production by specific CD4+ T cells was significantly reduced by tick saliva. And surprisingly, we have shown an inhibitory effect of tick saliva on the production of both Th1 (TNF-α and IL-6) and Th2 (IL-10) cytokines by DCs. Our data reveal a complex inhibitory effect of tick saliva on Borrelia-DCs interaction.