Open AccessSchistosomamansonitriggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses
Author(s) -
Manuel Ritter,
Olaf Groß,
Sarah Kays,
Jürgen Ruland,
Falk Nimmerjahn,
Shinobu Saijo,
Jürg Tschopp,
Laura E. Layland,
Clarissa Prazeres da Costa
Publication year - 2010
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1010337107
Subject(s) - inflammasome , biology , schistosoma mansoni , immune system , innate immune system , microbiology and biotechnology , antigen , signal transduction , immunology , acquired immune system , schistosomiasis , inflammation , helminths
The propensity of helminths, such as schistosomes, to immunomodulate the host's immune system is an essential aspect of their survival. Previous research has demonstrated how soluble schistosomal egg antigens (SEA) dampen TLR-signaling during innate immune responses. We show here that the suppressive effect by SEA on TLR signaling is simultaneously coupled to the activation of the Nlrp3 (NLR family, pyrin domain containing 3) inflammasome and thus IL-1β production. Therefore, the responsible protein component of SEA contains the second signal that is required to trigger proteolytic pro-IL-1β processing. Moreover, the SEA component binds to the Dectin-2/FcRγ (Fc receptor γ chain) complex and activates the Syk kinase signaling pathway to induce reactive oxygen species and potassium efflux. As IL-1β has been shown to be an essential orchestrator against several pathogens we studied the in vivo consequences ofSchistosoma mansoni infection in mice deficient in the central inflammasome adapter ASC and Nlrp3 molecule. These mice failed to induce local IL-1β levels in the liver and showed decreased immunopathology. Interestingly, antigen-specific Th1, Th2, and Th17 responses were down-regulated. Overall, these data imply that component(s) within SEA induce IL-1β production and unravel a crucial role of Nlrp3 duringS. mansoni infection.