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

Keira Melican, Jorrit Boekel, Lisa E. Månsson, Ruben M. Sandoval, George A. Tanner, Örjan Källskog, Fredrik Palm, Bruce A. Molitoris, Agneta Richter-Dahlfors

Research output: Contribution to journalArticlepeer-review

73 Scopus citations


Ascending urinary tract infections can cause extensive damage to kidney structure and function. We have used a number of advanced techniques including multiphoton microscopy to investigate the crucial early phases of uropathogenic Escherichia coli induced pyelonephritis within a living animal. Our results reveal a previously undescribed innate vascular response to mucosal infection, allowing isolation and eradication of the pathogen. The extremely rapid host response to mucosal infection was highlighted by the triggering of a cascade of events within 3-4 h. Epithelial signalling produced an increase in cellular O2 consumption and affected microvascular flow by clotting, causing localized ischaemia. Subsequent ischaemic damage affected pathophysiology with actin re-arrangement and epithelial sloughing leading to paracellular bacterial movement. A denuded tubular basement membrane is shown to hinder immediate dissemination of bacteria, giving the host time to isolate the infection by clotting. Suppression of clotting by heparin treatment caused fatal urosepsis. Clinically these findings may be relevant in antibiotics delivery in pyelonephritis patients and to the use of anticoagulants in sepsis.

Original languageEnglish (US)
Pages (from-to)1987-1998
Number of pages12
JournalCellular Microbiology
Issue number10
StatePublished - 2008

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

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