Your browser doesn't support javascript.
loading
NAIP-NLRC4-deficient mice are susceptible to shigellosis.
Mitchell, Patrick S; Roncaioli, Justin L; Turcotte, Elizabeth A; Goers, Lisa; Chavez, Roberto A; Lee, Angus Y; Lesser, Cammie F; Rauch, Isabella; Vance, Russell E.
Affiliation
  • 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.
  • Chavez RA; Broad Institute of Harvard and MIT, Cambridge, United States.
  • Lee AY; Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, United States.
  • Lesser CF; Division of Immunology & Pathogenesis, Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, United States.
  • Rauch I; Cancer Research Laboratory, University of California, Berkeley, Berkeley, United States.
  • Vance RE; Department of Microbiology, Harvard Medical School, Boston, United States.
Elife ; 92020 10 19.
Article in En | MEDLINE | ID: mdl-33074100
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.
Subject(s)
Key words

Full text: 1 Database: MEDLINE Main subject: Calcium-Binding Proteins / Disease Susceptibility / Dysentery, Bacillary / Apoptosis Regulatory Proteins / Neuronal Apoptosis-Inhibitory Protein Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Elife Year: 2020 Type: Article Affiliation country: United States

Full text: 1 Database: MEDLINE Main subject: Calcium-Binding Proteins / Disease Susceptibility / Dysentery, Bacillary / Apoptosis Regulatory Proteins / Neuronal Apoptosis-Inhibitory Protein Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Elife Year: 2020 Type: Article Affiliation country: United States