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Neurochemical Research - Neuroinflammation plays an important role in the pathophysiological process of acute cerebral infarction, which may aggravate brain injury and hinder neuro-repair.... 相似文献
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Parag Kundu Teo Wei Ling Agata Korecka Yinghui Li Rossana D'Arienzo Ralph M. Bunte Thorsten Berger Velmurugesan Arulampalam Pierre Chambon Tak Wah Mak Walter Wahli Sven Pettersson 《PLoS pathogens》2014,10(1)
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. 相似文献