Epithelial inflammasomes in the defense against Salmonella gut infection

• Published in: Current opinion in microbiology Vol. 59; pp. 86 - 94
• Main Authors: Fattinger, Stefan A, Sellin, Mikael E, Hardt, Wolf-Dietrich
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2021
• Subjects: cell death; enteropathogens; flagellum; inflammasomes; microbiology; Salmonella Typhimurium
• ISSN: 1369-5274; 1879-0364; 1879-0364
• DOI: 10.1016/j.mib.2020.09.014

•NAIP/NLRC4 and Caspase-4/11 inflammasomes restrict S.Tm infection of gut epithelium.•Importance of NAIP/NLRC4 versus Caspase-4/11 may shift between early and late infection.•Cell state and species-specific differences affect IEC inflammasome defense.•Interconnected inflammasome signalling may lead to apoptotic or lytic IEC expulsion. The gut epithelium prevents bacterial access to the host's tissues and coordinates a number of mucosal defenses. Here, we review the function of epithelial inflammasomes in the infected host and focus on their role in defense against Salmonella Typhimurium. This pathogen employs flagella to swim towards the epithelium and a type III secretion system (TTSS) to dock and invade intestinal epithelial cells. Flagella and TTSS components are recognized by the canonical NAIP/NLRC4 inflammasome, while LPS activates the non-canonical Caspase-4/11 inflammasome. The relative contributions of these inflammasomes, the activated cell death pathways and the elicited mucosal defenses are subject to environmental control and appear to change along the infection trajectory. It will be an important future task to explain how this may enable defense against the challenges imposed by diverse bacterial enteropathogens.