Group A streptococcal M protein activates the NLRP3 inflammasome.

ABSTRACT: Group A Streptococcus (GAS) is among the top ten causes of infection-related mortality in humans. M protein is the most abundant GAS surface protein, and M1 serotype GAS strains are associated with invasive infections, including necrotizing fasciitis and toxic shock syndrome. Here, we report that released, soluble M1 protein triggers programmed cell death in macrophages (Mϕ). M1 served as a second signal for caspase-1-dependent NLRP3 inflammasome activation, inducing maturation and release of proinflammatory cytokine interleukin-1β (IL-1β) and macrophage pyroptosis. The structurally dynamic B-repeat domain of M1 was critical for inflammasome activation, which involved K⁺ efflux and M1 protein internalization by clathrin-mediated endocytosis. Mouse intraperitoneal challenge showe

SUBMITTER: Valderrama JA 

PROVIDER: S-EPMC5750061 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature