Fas regulates neutrophil lifespan during viral and bacterial infection

Joanne A. O’Donnell, Catherine L. Kennedy, Marc Pellegrini, Cameron J. Nowell, Jian Guo Zhang, Lorraine A. O’Reilly, Louise Cengia, Stuart Dias, Seth L. Masters, Elizabeth L. Hartland, Andrew W. Roberts, Motti Gerlic, Ben A. Croker

Research output: Contribution to journalArticleResearchpeer-review

19 Citations (Scopus)

Abstract

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 Fasfl/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 neutr.

Original languageEnglish
Pages (from-to)321-326
Number of pages6
JournalJournal of leukocyte biology
Volume97
Issue number2
DOIs
Publication statusPublished - 1 Feb 2015
Externally publishedYes

Keywords

  • Apoptosis
  • Citrobacter rodentium
  • IL-18
  • LCMV
  • TLR

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