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 Molitoris, Agneta Richter-Dahlfors

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

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
Pages (from-to)1987-1998
Number of pages12
JournalCellular Microbiology
Volume10
Issue number10
DOIs
StatePublished - 2008

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Pathogens
Bacterial Infections
Anticoagulants
Escherichia coli
Heparin
Actins
Sepsis
Bacteria
Microscopic examination
Animals
Ischemia
Pyelonephritis
Anti-Bacterial Agents
Kidney
Infection
Uropathogenic Escherichia coli
Basement Membrane
Urinary Tract Infections
Blood Vessels
Microscopy

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Microbiology

Cite this

Melican, K., Boekel, J., Månsson, L. E., Sandoval, R. M., Tanner, G. A., Källskog, Ö., ... Richter-Dahlfors, A. (2008). Bacterial infection-mediated mucosal signalling induces local renal ischaemia as a defence against sepsis. Cellular Microbiology, 10(10), 1987-1998. https://doi.org/10.1111/j.1462-5822.2008.01182.x

Bacterial infection-mediated mucosal signalling induces local renal ischaemia as a defence against sepsis. / Melican, Keira; Boekel, Jorrit; Månsson, Lisa E.; Sandoval, Ruben M.; Tanner, George A.; Källskog, Örjan; Palm, Fredrik; Molitoris, Bruce; Richter-Dahlfors, Agneta.

In: Cellular Microbiology, Vol. 10, No. 10, 2008, p. 1987-1998.

Research output: Contribution to journalArticle

Melican, K, Boekel, J, Månsson, LE, Sandoval, RM, Tanner, GA, Källskog, Ö, Palm, F, Molitoris, B & Richter-Dahlfors, A 2008, 'Bacterial infection-mediated mucosal signalling induces local renal ischaemia as a defence against sepsis', Cellular Microbiology, vol. 10, no. 10, pp. 1987-1998. https://doi.org/10.1111/j.1462-5822.2008.01182.x
Melican, Keira ; Boekel, Jorrit ; Månsson, Lisa E. ; Sandoval, Ruben M. ; Tanner, George A. ; Källskog, Örjan ; Palm, Fredrik ; Molitoris, Bruce ; Richter-Dahlfors, Agneta. / Bacterial infection-mediated mucosal signalling induces local renal ischaemia as a defence against sepsis. In: Cellular Microbiology. 2008 ; Vol. 10, No. 10. pp. 1987-1998.
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