Open AccessCronobacter sakazakii induces necrotizing enterocolitis by regulating NLRP3 inflammasome expression via TLR4
Author(s) -
Zhenhui Chen,
Yiduo Zhang,
Ruqin Lin,
XiangJin Meng,
Wei Zhao,
Wei Shen,
Heng Fan
Publication year - 2020
Publication title -
journal of medical microbiology/journal of medical microbiology
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 0.91
H-Index - 117
eISSN - 1473-5644
pISSN - 0022-2615
DOI - 10.1099/jmm.0.001181
Subject(s) - necrotizing enterocolitis , cronobacter sakazakii , inflammasome , microbiology and biotechnology , enterocolitis , tlr4 , enterobacteriaceae infections , biology , enterobacteriaceae , medicine , infant formula , immunology , gene , inflammation , escherichia coli , food science , genetics
. Neonatal infection with Cronobacter sakazakii can cause severe intestinal damage and necrotizing enterocolitis (NEC). The inflammasome and Toll-like receptors mediate intestinal damage caused by other intestinal pathogens causing NEC, but the exact mechanism is unclear. Aim. We evaluated the molecular mechanisms underlying C. sakazakii -induced NEC. Methodology. The effects of C. sakazakii treatment on two cell lines and a Sprague-Dawley rat model of NEC were evaluated by a cell death assay, western blot and real-time PCR analyses of the NLRP3 inflammasome and downstream factors, and observation of cell and intestinal damage. Results. C. sakazakii caused cellular damage in vitro , as well as intestinal damage in an animal model. NLRP3, caspase-1, TLR4 and MyD88, as well as the downstream factor IL-1β, were upregulated in C. sakazakii -infected J774A.1 and HT-29 cells. Western blotting showed that C. sakazakii- infected J774A.1 and HT-29 cells and the NEC rat model had higher expression levels of N-terminal gasdermin D (GSDMD) compared with those in the control groups. C. sakazakii and its components promote NF-κB expression via the TLR4/MyD88 signalling pathway, thereby regulating the NLRP3 inflammasome and mediating GSDMD cleavage, resulting in pyroptosis-induced intestinal damage. Conclusion. We found that C. sakazakii upregulates NF-κB via TLR4/MyD88 to promote activation of the NLRP3 inflammasome, leading to the up-regulation of downstream caspase-1, release of IL-1β, GSDMD-mediated pyroptosis and development of NEC. These findings clarify the mechanisms by which C. sakazakii contributes to NEC.