title: The tick salivary protein sialostatin L2 inhibits caspase-1-mediated inflammation during Anaplasma phagocytophilum infection.
abstract: 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.
authors.affiliation: Center for Disease Vector Research and Department of Entomology, University of California, Riverside, California, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
authors.forename: Maiara S
authors.initials: MS
authors.lastname: Severo
authors.forename: Olivia S
authors.initials: OS
authors.lastname: Sakhon
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sohail
authors.forename: Lindsey J
authors.initials: LJ
authors.lastname: Brown
authors.forename: Mayukh
authors.initials: M
authors.lastname: Sircar
authors.forename: Greg A
authors.initials: GA
authors.lastname: Snyder
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Sundberg
authors.forename: Tyler K
authors.initials: TK
authors.lastname: Ulland
authors.forename: Alicia K
authors.initials: AK
authors.lastname: Olivier
authors.forename: John F
authors.initials: JF
authors.lastname: Andersen
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Shi
authors.forename: Fayyaz S
authors.initials: FS
authors.lastname: Sutterwala
authors.forename: Michail
authors.initials: M
authors.lastname: Kotsyfakis
authors.forename: Joao H F
authors.initials: JH
authors.lastname: Pedra
mesh_terms: D000704:Analysis of Variance; D041081:Anaplasma phagocytophilum / Q000502:physiology*; D000818:Animals; D020170:Caspase 1 / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D016873:Ehrlichiosis / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation / Q000503:physiopathology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D017382:Reactive Oxygen Species; D055333:Salivary Cystatins / Q000502:physiology*
chemical_list: D016207:Cytokines; D058847:Inflammasomes; D017382:Reactive Oxygen Species; D055333:Salivary Cystatins; D020170:Caspase 1