Skip to main content
Open Access Publications from the University of California

UC Riverside

UC Riverside Previously Published Works bannerUC Riverside

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

  • Author(s): Chen, Gang;
  • Wang, Xiaowei;
  • Severo, Maiara S.;
  • Sakhon, Olivia S.;
  • Sohail, Mohammad;
  • Brown, Lindsey J.;
  • Sircar, Mayukh;
  • Snyder, Greg A.;
  • Sundberg, Eric J.;
  • Ulland, Tyler K.;
  • Olivier, Alicia K.;
  • Andersen, John F.;
  • Zhou, Yi;
  • Shi, Guo-Ping;
  • Sutterwala, Fayyaz S.;
  • Kotsyfakis, Michail;
  • Pedra, Joao F.
  • et al.

Published Web Location
No data is associated with this publication.

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-1β (IL-1β) 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 κB 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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Item not freely available? Link broken?
Report a problem accessing this item