IL-33 deficiency inhibits Toxoplasma gondii infection by promoting NLRP3 inflammasome.

Abstract

NLRP3 inflammasome-mediated inflammatory responses play pivotal functions in innate immunity. However, its homeostatic regulation still needs to be better understood. Here we explore the effect and potential mechanism of IL-33 on NLRP3 inflammasome upon Toxoplasma gondii infection through a series of molecular biology and immunological experiments, including western blot, qRT-PCR, and ELISA. We demonstrated that T. gondii infection induces the expression of IL-33, and IL-33-deficient (IL-33^-/-) mice exhibit longer survival time than wild-type (WT) mice upon T. gondii infection. IL-33 deficiency promotes the expression of NLRP3 and ASC and the secretion of IL-1β, while exogenous IL-33 inhibits NLRP3 inflammasome. Furthermore, T. gondii infection results in the M2 polarization of macrophages, exacerbated by exogenous IL-33, which also promotes the proliferation of T. gondii. These findings showed that IL-33 deficiency attenuates T. gondii infection by promoting NLRP3 inflammasome, advancing the understanding of the role of IL-33 in inflammation.