Fas regulates neutrophil lifespan during viral and bacterial infection

J Leukoc Biol. 2015 Feb;97(2):321-6. doi: 10.1189/jlb.3AB1113-594RR. Epub 2014 Dec 3.


The regulation of neutrophil lifespan is critical for a circumscribed immune response. Neutrophils are sensitive to Fas/CD95 death receptor signaling in vitro, but it is unknown if Fas regulates neutrophil lifespan in vivo. We hypothesized that FasL-expressing CD8(+) T cells, which kill antigen-stimulated T cells during chronic viral infection, can also induce neutrophil death in tissues during infection. With the use of LysM-Cre Fas(fl/fl) mice, which lack Fas expression in macrophages and neutrophils, we show that Fas regulates neutrophil lifespan during lymphocytic choriomeningitis virus (LCMV) infection in the lung, peripheral blood, and spleen. Fas also contributed to the regulation of neutrophil numbers in the colon of Citrobacter rodentium-infected mice. To examine the effects of infection on Fas activation in neutrophils, we primed neutrophils with TLR ligands or IL-18, resulting in ablation of Fas death receptor signaling. These data provide the first in vivo genetic evidence that neutrophil lifespan is controlled by death receptor signaling and provide a mechanism to account for neutrophil resistance to Fas stimulation during infection.

Keywords: Citrobacter rodentium; IL-18; LCMV; TLR; apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Cellular Senescence / genetics
  • Cellular Senescence / immunology*
  • Citrobacter rodentium / immunology*
  • Enterobacteriaceae Infections / genetics
  • Enterobacteriaceae Infections / immunology*
  • Enterobacteriaceae Infections / pathology
  • Fas Ligand Protein / genetics
  • Fas Ligand Protein / immunology
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology*
  • Interleukin-18 / genetics
  • Interleukin-18 / immunology
  • Lymphocytic Choriomeningitis / genetics
  • Lymphocytic Choriomeningitis / immunology*
  • Lymphocytic Choriomeningitis / pathology
  • Lymphocytic choriomeningitis virus / immunology*
  • Macrophages / immunology
  • Macrophages / pathology
  • Mice
  • Mice, Knockout
  • Neutrophils / immunology*
  • Neutrophils / pathology
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • fas Receptor / genetics
  • fas Receptor / immunology*


  • Fas Ligand Protein
  • Fas protein, mouse
  • Fasl protein, mouse
  • Interleukin-18
  • fas Receptor