@article{8476327197414ab08c0429048e0b9c90,
title = "Naip–nlrc4-deficient mice are susceptible to shigellosis",
abstract = "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.",
author = "Mitchell, {Patrick S.} and Roncaioli, {Justin L.} and Turcotte, {Elizabeth A.} and Lisa Goers and Chavez, {Roberto A.} and Lee, {Angus Y.} and Lesser, {Cammie F.} and Isabella Rauch and Vance, {Russell E.}",
note = "Funding Information: We thank M Goldberg for advice and for sharing the icsA mutant Shigella strain. We are grateful to G Barton and H Darwin for comments on the manuscript, and members of the Vance and Barton Labs for discussions. Funding: REV is an HHMI Investigator and is supported by NIH AI075039 and AI063302; PSM is supported by a Jane Coffin Childs Memorial Fund postdoctoral fellowship. JLR is an Irving H Wiesenfeld CEND Fellow; EAT is supported by the UC Berkeley Department of Molecular and Cell Biology NIH Training Grant 5T32GM007232-42; CFL is a Brit d?Arbeloff MGH Research Scholar and supported by NIH AI064285 and NIH AI128743; IR is supported by the Medical Research Foundation MRF2012. Funding Information: We thank M Goldberg for advice and for sharing the icsA mutant Shigella strain. We are grateful to G Barton and H Darwin for comments on the manuscript, and members of the Vance and Barton Labs for discussions. Funding: REV is an HHMI Investigator and is supported by NIH AI075039 and AI063302; PSM is supported by a Jane Coffin Childs Memorial Fund postdoctoral fellowship. JLR is an Irving H Wiesenfeld CEND Fellow; EAT is supported by the UC Berkeley Department of Molecular and Cell Biology NIH Training Grant 5T32GM007232-42; CFL is a Brit d{\textquoteright}Arbeloff MGH Research Scholar and supported by NIH AI064285 and NIH AI128743; IR is supported by the Medical Research Foundation MRF2012. Publisher Copyright: {\textcopyright} Mitchell et al.",
year = "2020",
month = oct,
doi = "10.7554/eLife.59022",
language = "English (US)",
volume = "9",
pages = "1--25",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}