The Tick Salivary Protein Sialostatin L2 Inhibits Caspase-1-Mediated Inflammation during Anaplasma phagocytophilum Infection

0429372 - BC 2015 RIV US eng J - Journal Article
Chen, G. - Wang, X. - Sakhon, O. S. - Sohail, M. - Brown, L.J. - Sircar, M. - Snyder, G.A. - Sundberg, E.J. - Ulland, T.K. - Olivier, A.K. - Andersen, J. F. - Zhou, Y. - Shi, G.-P. - Sutterwala, F.S. - Kotsyfakis, Michalis - Pedra, J. H. F.
The Tick Salivary Protein Sialostatin L2 Inhibits Caspase-1-Mediated Inflammation during Anaplasma phagocytophilum Infection.
Infection and Immunity. Roč. 82, č. 6 (2014), s. 2553-2564. ISSN 0019-9567. E-ISSN 1098-5522
Institutional support: RVO:60077344
Keywords : granulocytic ehrlichiosis agent * Ixodes scapularis * tumor necrosis factor
Subject RIV: EC - Immunology
Impact factor: 3.731, year: 2014

Saliva from arthropod vectors facilitates blood feeding by altering host inflammation. Whether arthropod saliva counters inflammasome signaling, a protein scaffold that regulates the activity of caspase-1 and cleavage of interleukin-1 beta (IL-1 beta) and IL-18 into mature molecules, remains elusive. In this study, we provide evidence that a tick salivary protein, sialostatin L2, inhibits inflammasome formation during pathogen infection. We show that sialostatin L2 targets caspase-1 activity during host stimulation with the rickettsial agent Anaplasma phagocytophilum. A. phagocytophilum causes macrophage activation and hemophagocytic syndrome features. The effect of sialostatin L2 in macrophages was not due to direct caspase-1 enzymatic inhibition, and it did not rely on nuclear factor kappa B or cathepsin L signaling. Reactive oxygen species from NADPH oxidase and the Loop2 domain of sialostatin L2 were important for the regulatory process. Altogether, our data expand the knowledge of immunoregulatory pathways of tick salivary proteins and unveil an important finding in inflammasome biology.
Permanent Link: http://hdl.handle.net/11104/0234499