Pyroptosis and host cell death responses during Salmonella infection.
Salmonella enterica are facultatively intracellular pathogens causing diseases with markedly visible signs of inflammation. During infection, Salmonella interacts with various host cell types, often resulting in death of those cells. Salmonella induces intestinal epithelial cell death via apoptosis, a cell death programme with a notably non-inflammatory outcome. In contrast, macrophage infection triggers caspase-1-dependent proinflammatory programmed cell death, a recently recognized process termed pyroptosis, which is distinguished from other forms of cellular demise by its unique mechanism, features and inflammatory outcome. Rapid macrophage pyroptosis depends on the Salmonella pathogenicity island-1 type III secretion system (T3SS) and flagella. Salmonella dynamically modulates induction of macrophage pyroptosis, and regulation of T3SS systems permits bacterial replication in specialized intracellular niches within macrophages. However, these infected macrophages later undergo a delayed form of caspase-1-dependent pyroptosis. Caspase-1-deficient mice are more susceptible to a number of bacterial infections, including salmonellosis, and pyroptosis is therefore considered a generalized protective host response to infection. Thus, Salmonella-induced pyroptosis serves as a model to understand a broadly important pathway of proinflammatory programmed host cell death: examining this system affords insight into mechanisms of both beneficial and pathological cell death and strategies employed by pathogens to modulate host responses.
Fink
Susan L
SL
Molecular and Cellular Biology Program, University of Washington, Box 357110, 1959 N.E. Pacific Street, Seattle, WA 98195-7110, USA.
Cookson
Brad T
BT
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008954:Models, Biological; D012480:Salmonella Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D019779:Salmonella enterica / Q000276:immunology*