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

• Published in: Parasite immunology Vol. 37; no. 2; pp. 70 - 78
• Main Authors: Lieskovská, J., Páleníková, J., Širmarová, J., Elsterová, J., Kotsyfakis, M., Campos Chagas, A., Calvo, E., Růžek, D., Kopecký, J.
• Format: Journal Article
• Language: English
• Published: England 01.02.2015
• Subjects: Animals; Borrelia burgdorferi - physiology; cystatin; Cystatins - immunology; dendritic cell; Dendritic Cells - immunology; Female; interferon; Interferon Regulatory Factor-7 - immunology; Interferon-beta - immunology; Ixodes - immunology; Ixodes - microbiology; Lipopolysaccharides - immunology; Mice; Mice, Inbred C57BL; Phosphorylation; Receptors, Cytokine - immunology; Receptors, Interferon - metabolism; Salivary Cystatins - immunology; tick; cystatin; tick; interferon; dendritic cell
• ISSN: 0141-9838; 1365-3024
• DOI: 10.1111/pim.12162

Summary 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.