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Microbiota Normalization Reveals that Canonical Caspase-1 Activation Exacerbates Chemically Induced Intestinal Inflammation.

Błażejewski, Adrian J
; 
Thiemann, Sophie
; 
Schenk, Alexander
; 
Pils, Marina C
; 
Gálvez, Eric J C
; 
Roy, Urmi
; 
Heise, Ulrike
; 
de Zoete, Marcel R
; 
Flavell, Richard A
; 
Strowig, Till
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2017-06-13
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Abstract
Inflammasomes play a central role in regulating intestinal barrier function and immunity during steady state and disease. Because the discoveries of a passenger mutation and a colitogenic microbiota in the widely used caspase-1-deficient mouse strain have cast doubt on previously identified direct functions of caspase-1, we reassessed the role of caspase-1 in the intestine. To this end, we generated Casp1(-/-) and Casp11(-/-) mice and rederived them into an enhanced barrier facility to standardize the microbiota. We found that caspase-11 does not influence caspase-1-dependent processing of IL-18 in homeostasis and during DSS colitis. Deficiency of caspase-1, but not caspase-11, ameliorated the severity of DSS colitis independent of microbiota composition. Ablation of caspase-1 in intestinal epithelial cells was sufficient to protect mice against DSS colitis. Moreover, Casp1(-/-) mice developed fewer inflammation-induced intestinal tumors than control mice. These data show that canonical inflammasome activation controls caspase-1 activity, contributing to exacerbation of chemical-induced colitis.
Citation
Microbiota Normalization Reveals that Canonical Caspase-1 Activation Exacerbates Chemically Induced Intestinal Inflammation. 2017, 19 (11):2319-2330 Cell Rep
Affiliation
Helmholtz Centre for infection research, Inhoffenstr. 7. 38124 Braunschweig, Germany.
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Cell reports
URI
http://hdl.handle.net/10033/621026
DOI
10.1016/j.celrep.2017.05.058
PubMed ID
28614717
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Article
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en
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2211-1247
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publications of the research group microbial immunoregulation (MIKI)
publications of the junior research group infection biology of Salmonella (IBIS)
publications of the research group of experimental infection research([TC] EXPI)
publications of the service unit animal experimentation: (TEE)