Journal article
Noncanonical inflammasome activation of caspase-4/caspase-11 mediates epithelial defenses against enteric bacterial pathogens
Cell host & microbe, Vol.16(2), pp.249-256
08/13/2014
Handle:
https://hdl.handle.net/2376/117389
PMID: 25121752
Abstract
Inflammasome-mediated host defenses have been extensively studied in innate immune cells. Whether inflammasomes function for innate defense in intestinal epithelial cells, which represent the first line of defense against enteric pathogens, remains unknown. We observed enhanced Salmonella enterica serovar Typhimurium colonization in the intestinal epithelium of caspase-11-deficient mice, but not at systemic sites. In polarized epithelial monolayers, siRNA-mediated depletion of caspase-4, a human ortholog of caspase-11, also led to increased bacterial colonization. Decreased rates of pyroptotic cell death, a host defense mechanism that extrudes S. Typhimurium-infected cells from the polarized epithelium, accounted for increased pathogen burdens. The caspase-4 inflammasome also governs activation of the proinflammatory cytokine, interleukin (IL)-18, in response to intracellular (S. Typhimurium) and extracellular (enteropathogenic Escherichia coli) enteric pathogens, via intracellular LPS sensing. Therefore, an epithelial cell-intrinsic noncanonical inflammasome plays a critical role in antimicrobial defense at the intestinal mucosal surface.
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Details
- Title
- Noncanonical inflammasome activation of caspase-4/caspase-11 mediates epithelial defenses against enteric bacterial pathogens
- Creators
- Leigh A Knodler - Paul G. Allen School for Global Animal Health, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-7090, USA; Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT 59840, USA. Electronic address: lknodler@vetmed.wsu.eduShauna M Crowley - Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver BC V6H 3V4, CanadaHo Pan Sham - Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver BC V6H 3V4, CanadaHyungjun Yang - Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver BC V6H 3V4, CanadaMarie Wrande - Paul G. Allen School for Global Animal Health, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-7090, USACaixia Ma - Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver BC V6H 3V4, CanadaRobert K Ernst - Department of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, MD 21201, USAOlivia Steele-Mortimer - Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT 59840, USAJean Celli - Paul G. Allen School for Global Animal Health, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-7090, USA; Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT 59840, USABruce A Vallance - Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver BC V6H 3V4, Canada. Electronic address: bvallance@cw.bc.ca
- Publication Details
- Cell host & microbe, Vol.16(2), pp.249-256
- Academic Unit
- Paul G. Allen School for Global Animal Health
- Publisher
- United States
- Grant note
- Canadian Institutes of Health Research ZIA AI000954-09 / Intramural NIH HHS ZIA AI001111-05 / Intramural NIH HHS
- Identifiers
- 99900548174401842
- Language
- English
- Resource Type
- Journal article