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Title: Absence of Intestinal PPARγ Aggravates Acute Infectious Colitis in Mice through a Lipocalin-2-Dependent Pathway
Authors: Kundu, P.
Ling, T.W.
Korecka, A.
Li, Y.
D'Arienzo, R.
Bunte, R.M. 
Berger, T.
Arulampalam, V.
Chambon, P.
Mak, T.W.
Wahli, W.
Pettersson, S.
Issue Date: Jan-2014
Citation: Kundu, P., Ling, T.W., Korecka, A., Li, Y., D'Arienzo, R., Bunte, R.M., Berger, T., Arulampalam, V., Chambon, P., Mak, T.W., Wahli, W., Pettersson, S. (2014-01). Absence of Intestinal PPARγ Aggravates Acute Infectious Colitis in Mice through a Lipocalin-2-Dependent Pathway. PLoS Pathogens 10 (1) : -. ScholarBank@NUS Repository.
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. © 2014 Kundu et al.
Source Title: PLoS Pathogens
ISSN: 15537366
DOI: 10.1371/journal.ppat.1003887
Appears in Collections:Staff Publications

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