title: Tick salivary cystatin sialostatin L2 suppresses IFN responses in mouse dendritic cells.
abstract: 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.
authors.affiliation: Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic; Institute of Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic, České Budějovice, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Lieskovská
authors.forename: J
authors.initials: J
authors.lastname: Páleníková
authors.forename: J
authors.initials: J
authors.lastname: Širmarová
authors.forename: J
authors.initials: J
authors.lastname: Elsterová
authors.forename: M
authors.initials: M
authors.lastname: Kotsyfakis
authors.forename: A
authors.initials: A
authors.lastname: Campos Chagas
authors.forename: E
authors.initials: E
authors.lastname: Calvo
authors.forename: D
authors.initials: D
authors.lastname: Růžek
authors.forename: J
authors.initials: J
authors.lastname: Kopecký
mesh_terms: D000818:Animals; D025065:Borrelia burgdorferi / Q000502:physiology*; D015891:Cystatins / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D050839:Interferon Regulatory Factor-7 / Q000276:immunology; D016899:Interferon-beta / Q000276:immunology*; D018884:Ixodes / Q000276:immunology* / Q000382:microbiology; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D018121:Receptors, Cytokine / Q000276:immunology; D017471:Receptors, Interferon / Q000378:metabolism; D055333:Salivary Cystatins / Q000276:immunology*
chemical_list: D015891:Cystatins; C104577:IP10-Mig receptor; D050839:Interferon Regulatory Factor-7; C494235:Irf7 protein, mouse; D008070:Lipopolysaccharides; D018121:Receptors, Cytokine; D017471:Receptors, Interferon; D055333:Salivary Cystatins; C515505:sialostatin L, Ixodes scapularis; D016899:Interferon-beta
keywords: cystatin; dendritic cell; interferon; tick