The tick protein sialostatin L2 binds to annexin A2 and inhibits NLRC4-mediated inflammasome activation

Xiaowei Wang, Dana K. Shaw, Olivia S. Sakhon, Greg A. Snyder, Eric J. Sundberg, Laura Santambrogio, Fayyaz S. Sutterwala, J. Stephen Dumler, Kari Ann Shirey, Darren J. Perkins, Katharina Richard, Andrezza C. Chagas, Eric Calvo, Jan Kopecký, Michail Kotsyfakis, Joao H F Pedra

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Tick saliva contains a number of effector molecules that inhibit host immunity and facilitate pathogen transmission. How tick proteins regulate immune signaling, however, is incompletely understood. Here, we describe that loop 2 of sialostatin L2, an anti-inflammatory tick protein, binds to annexin A2 and impairs the formation of the NLRC4 inflammasome during infection with the rickettsial agent Anaplasma phagocytophilum. Macrophages deficient in annexin A2 secreted significantly smaller amounts of interleukin-β (IL-β) and IL-18 and had a defect in NLRC4 inflammasome oligomerization and caspase-1 activation. Accordingly, Annexin a2-deficient mice were more susceptible to A. phagocytophilum infection and showed splenomegaly, thrombocytopenia, and monocytopenia. Providing translational support to our findings, better binding of annexin A2 to sialostatin L2 in sera from 21 out of 23 infected patients than in sera from control individuals was also demonstrated. Overall, we establish a unique mode of inflammasome evasion by a pathogen, centered on a blood-feeding arthropod.

Original languageEnglish (US)
Pages (from-to)1796-1805
Number of pages10
JournalInfection and Immunity
Volume84
Issue number6
DOIs
StatePublished - Jun 1 2016

    Fingerprint

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Wang, X., Shaw, D. K., Sakhon, O. S., Snyder, G. A., Sundberg, E. J., Santambrogio, L., Sutterwala, F. S., Stephen Dumler, J., Shirey, K. A., Perkins, D. J., Richard, K., Chagas, A. C., Calvo, E., Kopecký, J., Kotsyfakis, M., & Pedra, J. H. F. (2016). The tick protein sialostatin L2 binds to annexin A2 and inhibits NLRC4-mediated inflammasome activation. Infection and Immunity, 84(6), 1796-1805. https://doi.org/10.1128/IAI.01526-15