Please use this identifier to cite or link to this item:
|Title:||Absence of Intestinal PPARγ Aggravates Acute Infectious Colitis in Mice through a Lipocalin-2-Dependent Pathway||Authors:||Kundu, P.
|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. https://doi.org/10.1371/journal.ppat.1003887||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||URI:||http://scholarbank.nus.edu.sg/handle/10635/110483||ISSN:||15537366||DOI:||10.1371/journal.ppat.1003887|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
|2014-absence_intestinal_PPARy_aggravates_acute-published.pdf||4.74 MB||Adobe PDF|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.