Uropathogenic Escherichia coli engages CD14-dependent signaling to enable bladder macrophage-dependent control of acute urinary tract infection

作者: Alison J. Carey , Matthew J. Sullivan , Benjamin L. Duell , David K. Crossman , Debasish Chattopadhyay

DOI: 10.1093/INFDIS/JIV424

关键词: CD14MonocytePattern recognition receptorBiologyLipopolysaccharideCytokineMacrophageImmune systemMicrobiologyEscherichia coliImmunology

摘要: Background. CD14, a coreceptor for several pattern recognition receptors and widely used monocyte/macrophage marker, plays key role in host responses to gram-negative bacteria. Despite the central of CD14 inflammatory response lipopolysaccharide other microbial products dissemination bacteria some infections, signaling networks controlled by during urinary tract infection (UTI) are unknown. Methods. We uropathogenic Escherichia coli (UPEC) wild-type (WT) C57BL/6 Cd14-/- mice RNA sequencing define CD14-dependent transcriptional signature defense against UTI bladder. Results. UPEC induced upregulation Cd14 monocyte/macrophage-related genes Emr1/F4/80 Csf1r/c-fms, which was associated with lower burdens WT mice, compared mice. Exacerbation absence 491-gene bladder that encompassed multiple not previously this receptor. pathways included immune cell trafficking, differential cytokine production macrophages, interleukin 17 signaling. Depletion monocytes/macrophages administration liposomal clodronate led higher burdens. Conclusions. This study identifies new protective roles UTI. (Less)

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