Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/80010
Title: Absence of intestinal PPARγ aggravates acute infectious colitis in mice through a Lipocalin-2–dependent pathway
Authors: Bunte, Ralph M.
Kundu, Parag
Ling, Teo Wei
Korecka, Agata
Li, Yinghui
D'Arienzo, Rossana
Berger, Thorsten
Arulampalam, Velmurugesan
Chambon, Pierre
Mak, Tak Wah
Wahli, Walter
Pettersson, Sven
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
http://hdl.handle.net/10220/18858
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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