期刊
IMMUNITY
卷 46, 期 4, 页码 649-659出版社
CELL PRESS
DOI: 10.1016/j.immuni.2017.03.016
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类别
资金
- HHMI
- NIH [AI075039, AI063302, EY026082, 1S10RR026866-01]
- Austrian Science Fund (FWF) (the Erwin Schrodinger Fellowship) [J3789-B22]
- Austrian Science Fund (FWF) [J3789] Funding Source: Austrian Science Fund (FWF)
- Austrian Science Fund (FWF) [J 3789] Funding Source: researchfish
Intestinal epithelial cells (IECs) form a critical barrier against pathogen invasion. By generation of mice in which inflammasome expression is restricted to IECs, we describe a coordinated epithelium-intrinsic inflammasome response in vivo. This response was sufficient to protect against Salmonella tissue invasion and involved a previously reported IEC expulsion that was coordinated with lipid mediator and cytokine production and lytic IEC death. Excessive inflammasome activation in IECs was sufficient to result in diarrhea and pathology. Experiments with IEC organoids demonstrated that IEC expulsion did not require other cell types. IEC expulsion was accompanied by a major actin rearrangement in neighboring cells that maintained epithelium integrity but did not absolutely require Caspase-1 or Gasdermin D. Analysis of Casp1(-/-)Casp8(-/-) mice revealed a functional Caspase-8 inflammasome in vivo. Thus, a coordinated IEC-intrinsic, Caspase-1 and -8 inflammasome response plays a key role in intestinal immune defense and pathology.
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