The inhibitory receptor CD300a is essential for neutrophil-mediated clearance of urinary tract infection in mice

Eur J Immunol. 2021 Sep;51(9):2218-2224. doi: 10.1002/eji.202049006. Epub 2021 Aug 2.

Abstract

Neutrophils play a crucial role in immune defense against and clearance of uropathogenic Escherichia coli (UPEC)-mediated urinary tract infection, the most common bacterial infection in healthy humans. CD300a is an inhibitory receptor that binds phosphatidylserine and phosphatidylethanolamine, presented on the membranes of apoptotic cells. CD300a binding to phosphatidylserine and phosphatidylethanolamine, also known as the "eat me" signal, mediates immune tolerance to dying cells. Here, we demonstrate for the first time that CD300a plays an important role in the neutrophil-mediated immune response to UPEC-induced urinary tract infection. We show that CD300a-deficient neutrophils have impaired phagocytic abilities and despite their increased accumulation at the site of infection, they are unable to reduce bacterial burden in the bladder, which results in significant exacerbation of infection and worse host outcome. Finally, we demonstrate that UPEC's pore forming toxin α-hemolysin induces upregulation of the CD300a ligand on infected bladder epithelial cells, signaling to neutrophils to be cleared.

Keywords: CD300a; Epithelial cells; Neutrophils; Urinary tract infection; α-hemolysin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Escherichia coli Infections / immunology
  • Escherichia coli Infections / prevention & control*
  • Escherichia coli Proteins / metabolism
  • Female
  • Gene Knockout Techniques
  • Hemolysin Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Neutrophils / immunology*
  • Phagocytosis / genetics
  • Phagocytosis / immunology
  • Phosphatidylethanolamines / metabolism
  • Phosphatidylserines / metabolism
  • Receptors, Immunologic / deficiency*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology*
  • Urinary Bladder / immunology
  • Urinary Bladder / microbiology
  • Urinary Bladder / pathology
  • Urinary Tract Infections / immunology*
  • Urinary Tract Infections / microbiology
  • Uropathogenic Escherichia coli / growth & development
  • Uropathogenic Escherichia coli / immunology*

Substances

  • Escherichia coli Proteins
  • Hemolysin Proteins
  • Hlya protein, E coli
  • LMIR1 protein, mouse
  • Phosphatidylethanolamines
  • Phosphatidylserines
  • Receptors, Immunologic
  • phosphatidylethanolamine