Role of Hypoxia Inducible Factor-1α (HIF-1α) in Innate Defense against Uropathogenic Infection

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Urinary tract infection (UTI), commonly caused by uropathogenic E.coli (UPEC), affects more than 150 million people worldwide, resulting in 14 million hospital visits per year and an estimated total cost of 6 billion dollars in direct health care. Due to the high prevalence of UTI and rapid emergence of antibiotic-resistant bacteria, new effective strategies to prevent and treat UTI are urgently needed. Here, we describe a global regulatory role of transcription factor hypoxia-inducible factor-1 (HIF-1) in innate antimicrobial defense against UPEC. HIF-1 stabilization reduces UPEC attachment to and invasion of uroepithelial cells, and protects bladders from UPEC-mediated cytotoxicity in vivo. In the murine UTI model, we found normal bladder HIF-1 expression is required for efficient UPEC clearance, since HIF-1-deficient mice suffer more severe infection than normal mice. Further studies showed that key elements of host protection provided by HIF-1 regulation are uroepithelial cell nitric oxide and antimicrobial peptide production. This study provides valuable insight into the importance of HIF-1 in supporting host immunity during UTI and its potential as a therapeutic target.

Vyšlo v časopise: Role of Hypoxia Inducible Factor-1α (HIF-1α) in Innate Defense against Uropathogenic Infection. PLoS Pathog 11(4): e32767. doi:10.1371/journal.ppat.1004818
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004818

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