| First Author | Kundu P | Year | 2014 |
| Journal | PLoS Pathog | Volume | 10 |
| Issue | 1 | Pages | e1003887 |
| PubMed ID | 24465207 | Mgi Jnum | J:242057 |
| Mgi Id | MGI:5904247 | Doi | 10.1371/journal.ppat.1003887 |
| Citation | Kundu P, et al. (2014) Absence of intestinal PPARgamma aggravates acute infectious colitis in mice through a lipocalin-2-dependent pathway. PLoS Pathog 10(1):e1003887 |
| abstractText | 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 (PPARgamma) expression in intestinal epithelial cells. Interestingly, this PPARgamma 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 PPARgamma and Lcn2 to acquire residence in a host, which by evolution has established a symbiotic relation with its microbiome community to prevent pathogen invasion. |
