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|Title:||Absence of intestinal PPARγ aggravates acute infectious colitis in mice through a Lipocalin-2–dependent pathway||Authors:||Bunte, Ralph M.
Ling, Teo Wei
Mak, Tak Wah
|Keywords:||DRNTU::Science::General||Issue Date:||2014||Source:||Kundu, P., Ling, T. W., Korecka, A., Li, Y., D'Arienzo, R., Bunte, R. M., et al. (2014). Absence of Intestinal PPARγ Aggravates Acute Infectious Colitis in Mice through a Lipocalin-2–Dependent Pathway. PLoS Pathogens, 10(1), e1003887-.||Series/Report no.:||PLoS pathogens||Abstract:||To be able to colonize its host, invading Salmonella enterica serovar Typhimurium must disrupt and severely affect host-microbiome homeostasis. Here we report that S. Typhimurium induces acute infectious colitis by inhibiting peroxisome proliferator-activated receptor gamma (PPARγ) expression in intestinal epithelial cells. Interestingly, this PPARγ down-regulation by S. Typhimurium is independent of TLR-4 signaling but triggers a marked elevation of host innate immune response genes, including that encoding the antimicrobial peptide lipocalin-2 (Lcn2). Accumulation of Lcn2 stabilizes the metalloproteinase MMP-9 via extracellular binding, which further aggravates the colitis. Remarkably, when exposed to S. Typhimurium, Lcn2-null mice exhibited a drastic reduction of the colitis and remained protected even at later stages of infection. Our data suggest a mechanism in which S. Typhimurium hijacks the control of host immune response genes such as those encoding PPARγ and Lcn2 to acquire residence in a host, which by evolution has established a symbiotic relation with its microbiome community to prevent pathogen invasion.||URI:||https://hdl.handle.net/10356/80010
|ISSN:||1553-7374||DOI:||10.1371/journal.ppat.1003887||Rights:||© 2014 Kundu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||LKCMedicine Journal Articles|
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