Inflammasome and gasdermin signaling in neutrophils.

Inflammasomes and gasdermins mount potent host defense pathways against invading microbial pathogens, however, dysregulation in these pathways can drive a variety of inflammatory disorders. Neutrophils, historically regarded as effector phagocytes that drive host defense via microbial killing, are now emerging as critical drivers of immunity in vivo. Here, we summarize, the latest advancement in inflammasome, gasdermin, and cell death signaling in neutrophils. We discuss the mechanisms by which neutrophils resist caspase-1-dependent pyroptosis, the lytic function of gasdermin D and E during NETosis and Yersinia infection, and the contribution of neutrophil inflammasomes to inflammatory disorders.

RIPK1 and RIPK3 in antibacterial defence.

Upon sensing pathogenic bacterial infection, host cells activate a multitude of inflammatory and immunogenic responses to promote bacterial clearance and restore tissue homeostasis. RIPK1 and RIPK3 are two key players in antimicrobial defence, by either driving inflammatory signalling or inducing programmed cell death activation, ranging from apoptosis, pyroptosis to necroptosis. In this review, we first discuss the mechanisms by which RIPK1 and RIPK3 promote the assembly of death-inducing complexes and how these cell death pathways are activated as host responses to counteract pathogenic bacteria. We further outline the immunological importance of cell death in antibacterial defence and highlight outstanding questions in the field.