Stromal Cell-Derived Factor 1 Mediates Immune Cell Attraction upon Urinary Tract Infection

Cell Rep. 2017 Jul 5;20(1):40-47. doi: 10.1016/j.celrep.2017.06.034.

Abstract

Urinary tract infection (UTI) is the most common type of bacterial infection in humans. Fifty percent of all women will experience at least one UTI in their lifetime, with uropathogenic Escherichia coli (UPEC) accounting for 80% of reported cases. UTI evokes a complex, well-timed immune response that is crucial for bacterial clearance. The majority of immune cells participating in the immune response are absent from the healthy bladder, and the mechanisms used to recruit them upon UTI are not fully understood. Here, we show that immediately after UPEC infection, bladder epithelial cells secrete stromal cell-derived factor 1 (SDF-1), initiating immune cell accumulation at the site of infection. SDF-1 blockade significantly reduced immune cell migration to the infected bladder, resulting in severe exacerbation of infection. We also show that FimH, the adhesin of type 1 fimbria, one of UPEC's virulence factors, is directly involved in the secretion of SDF-1 upon UTI.

Keywords: SDF1; UPEC; UTI; innate cells.

MeSH terms

  • Adhesins, Escherichia coli / immunology
  • Animals
  • Chemokine CXCL12 / immunology*
  • Chemokine CXCL12 / metabolism
  • Enteropathogenic Escherichia coli / immunology
  • Enteropathogenic Escherichia coli / pathogenicity
  • Female
  • Fimbriae Proteins / immunology
  • Immunity, Innate*
  • Killer Cells, Natural / immunology
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / immunology
  • T-Lymphocytes / immunology
  • Urinary Tract Infections / immunology*
  • Urinary Tract Infections / microbiology
  • Urothelium / immunology
  • Urothelium / metabolism

Substances

  • Adhesins, Escherichia coli
  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • fimH protein, E coli
  • Fimbriae Proteins