Protective vascular coagulation in response to bacterial infection of the kidney is regulated by bacterial lipid A and host CD147

Anette Schulz, Olga D. Chuquimia, Haris Antypas, Svava E. Steiner, Ruben M. Sandoval, George A. Tanner, Bruce A. Molitoris, Agneta Richter-Dahlfors, Keira Melican

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Bacterial infection of the kidney leads to a rapid cascade of host protective responses, many of which are still poorly understood. We have previously shown that following kidney infection with uropathogenic Escherichia coli (UPEC), vascular coagulation is quickly initiated in local perivascular capillaries that protects the host from progressing from a local infection to systemic sepsis. The signaling mechanisms behind this response have not however been described. In this study, we use a number of in vitro and in vivo techniques, including intravital microscopy, to identify two previously unrecognized components influencing this protective coagulation response. The acylation state of the Lipid A of UPEC lipopolysaccharide (LPS) is shown to alter the kinetics of local coagulation onset in vivo. We also identify epithelial CD147 as a potential host factor influencing infection-mediated coagulation. CD147 is expressed by renal proximal epithelial cells infected with UPEC, contingent to bacterial expression of the α-hemolysin toxin. The epithelial CD147 subsequently can activate tissue factor on endothelial cells, a primary step in the coagulation cascade. This study emphasizes the rapid, multifaceted response of the kidney tissue to bacterial infection and the interplay between host and pathogen during the early hours of renal infection.

Original languageEnglish (US)
Article numberfty087
JournalPathogens and Disease
Volume76
Issue number8
DOIs
StatePublished - Nov 1 2018

Keywords

  • CD147
  • Escherichia coli
  • UPEC
  • UTI
  • coagulation
  • kidney
  • lipid A
  • tissue microbiology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology and Microbiology(all)
  • Microbiology (medical)
  • Infectious Diseases

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    Schulz, A., Chuquimia, O. D., Antypas, H., Steiner, S. E., Sandoval, R. M., Tanner, G. A., Molitoris, B. A., Richter-Dahlfors, A., & Melican, K. (2018). Protective vascular coagulation in response to bacterial infection of the kidney is regulated by bacterial lipid A and host CD147. Pathogens and Disease, 76(8), [fty087]. https://doi.org/10.1093/femspd/fty087