NAIP-NLRC4-deficient mice are susceptible to shigellosis.

Autor:	Mitchell PS; Division of Immunology & Pathogenesis, Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, United States., Roncaioli JL; Division of Immunology & Pathogenesis, Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, United States., Turcotte EA; Division of Immunology & Pathogenesis, Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, United States., Goers L; Department of Microbiology, Harvard Medical School, Boston, United States.; Broad Institute of Harvard and MIT, Cambridge, United States.; Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, United States., Chavez RA; Division of Immunology & Pathogenesis, Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, United States., Lee AY; Cancer Research Laboratory, University of California, Berkeley, Berkeley, United States., Lesser CF; Department of Microbiology, Harvard Medical School, Boston, United States.; Broad Institute of Harvard and MIT, Cambridge, United States.; Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, United States., Rauch I; Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, United States., Vance RE; Division of Immunology & Pathogenesis, Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, United States.; Cancer Research Laboratory, University of California, Berkeley, Berkeley, United States.; Immunotherapeutics and Vaccine Research Initiative, University of California, Berkeley, Berkeley, United States.; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2020 Oct 19; Vol. 9. Date of Electronic Publication: 2020 Oct 19.
DOI:	10.7554/eLife.59022
Abstrakt:	Bacteria of the genus Shigella cause shigellosis, a severe gastrointestinal disease that is a major cause of diarrhea-associated mortality in humans. Mice are highly resistant to Shigella and the lack of a tractable physiological model of shigellosis has impeded our understanding of this important human disease. Here, we propose that the differential susceptibility of mice and humans to Shigella is due to mouse-specific activation of the NAIP-NLRC4 inflammasome. We find that NAIP-NLRC4-deficient mice are highly susceptible to oral Shigella infection and recapitulate the clinical features of human shigellosis. Although inflammasomes are generally thought to promote Shigella pathogenesis, we instead demonstrate that intestinal epithelial cell (IEC)-specific NAIP-NLRC4 activity is sufficient to protect mice from shigellosis. In addition to describing a new mouse model of shigellosis, our results suggest that the lack of an inflammasome response in IECs may help explain the susceptibility of humans to shigellosis. Competing Interests: PM, JR, ET, LG, RC, AL, CL, IR No competing interests declared, RV Reviewing editor, eLife (© 2020, Mitchell et al.)
Databáze:	MEDLINE
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