Bacterial infection-mediated mucosal signalling induces local renal ischaemia as a defence against sepsis

摘要: Ascending urinary tract infections can cause extensive damage to kidney structure and function. We have used a number of advanced techniques including multiphoton microscopy investigate the crucial early phases uropathogenic Escherichia coli induced pyelonephritis within living animal. Our results reveal previously undescribed innate vascular response mucosal infection, allowing isolation eradication pathogen. The extremely rapid host infection was highlighted by triggering cascade events 3-4 h. Epithelial signalling produced an increase in cellular O(2) consumption affected microvascular flow clotting, causing localized ischaemia. Subsequent ischaemic pathophysiology with actin re-arrangement epithelial sloughing leading paracellular bacterial movement. A denuded tubular basement membrane is shown hinder immediate dissemination bacteria, giving time isolate clotting. Suppression clotting heparin treatment caused fatal urosepsis. Clinically these findings may be relevant antibiotics delivery patients use anticoagulants sepsis.