Formylpeptide receptors are critical for rapid neutrophil mobilization in host defense against Listeria monocytogenes

Sci Rep. 2012;2:786. doi: 10.1038/srep00786. Epub 2012 Nov 8.

Abstract

Listeria monocytogenes (Listeria) causes opportunistic infection in immunocompromised hosts with high mortality. Resistance to Listeria depends on immune responses and recruitment of neutrophils of the immune system into infected sites is an early and critical step. Mouse neutrophils express two G protein-coupled formylpeptide receptor subtypes Fpr1 and Fpr2 that recognize bacterial and host-derived chemotactic molecules including Listeria peptides for cell migration and activation. Here we report deficiency in Fprs exacerbated the severity of the infection and increased the mortality of infected mice. The mechanism involved impaired early neutrophil recruitment to the liver with Fpr1 and Fpr2 being sole receptors for neutrophils to sense Listeria chemoattractant signals and for production of bactericidal superoxide. Thus, Fprs are essential sentinels to guide the first wave of neutrophil infiltration in the liver of Listeria-infected mice for effective elimination of the invading pathogen.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Movement
  • Chemokines / metabolism
  • Chemotaxis
  • HEK293 Cells
  • Humans
  • Hydrogen Peroxide / metabolism
  • Listeria monocytogenes / immunology
  • Listeria monocytogenes / pathogenicity*
  • Listeriosis / microbiology
  • Listeriosis / mortality
  • Listeriosis / pathology
  • Liver / metabolism
  • Liver / microbiology
  • Mice
  • Mice, Knockout
  • Neutrophil Infiltration
  • Neutrophils / immunology
  • Neutrophils / metabolism*
  • Phagocytosis
  • Receptors, Formyl Peptide / deficiency
  • Receptors, Formyl Peptide / genetics
  • Receptors, Formyl Peptide / metabolism*

Substances

  • Chemokines
  • Fpr1 protein, mouse
  • Receptors, Formyl Peptide
  • formyl peptide receptor 2, mouse
  • Hydrogen Peroxide