Absence of intestinal PPARγ aggravates acute infectious colitis in mice through a lipocalin-2-dependent pathway.

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Ressource 1Télécharger: BIB_7663DC986070.P001.pdf (4742.25 [Ko])
Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_7663DC986070
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Absence of intestinal PPARγ aggravates acute infectious colitis in mice through a lipocalin-2-dependent pathway.
Périodique
PLoS Pathogens
Auteur(s)
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.
ISSN
1553-7374 (Electronic)
ISSN-L
1553-7366
Statut éditorial
Publié
Date de publication
2014
Volume
10
Numéro
1
Pages
e1003887
Langue
anglais
Résumé
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.
Pubmed
Web of science
Open Access
Oui
Création de la notice
01/05/2014 14:02
Dernière modification de la notice
08/05/2019 20:33
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