Journal article

Fas regulates neutrophil lifespan during viral and bacterial infection

JA O’Donnell, CL Kennedy, M Pellegrini, CJ Nowell, JG Zhang, LA O’Reilly, L Cengia, S Dias, SL Masters, EL Hartland, AW Roberts, M Gerlic, BA Croker

Journal of Leukocyte Biology | Published : 2015

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 neut..

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Grants

Awarded by NHMRC


Awarded by Australian National Health and Medical Research Council (NHMRC) from the NHMRC


Awarded by Independent Research Institutes Infrastructure Support Scheme Grant from the NHMRC


Awarded by Leukemia and Lymphoma Society


Funding Acknowledgements

This work was supported by project grants (637367, 1045532, and 1009145), program grants (461219, 1016647, 461221, 1016701, and 606788), a Australian National Health and Medical Research Council (NHMRC) Practitioner Fellowship to A.W.R. (637309), a Dora Lush Scholarship (to J.A.O.), a Discovery Early Career Researcher Award (to C.L.K), and an Independent Research Institutes Infrastructure Support Scheme Grant (361646) from the NHMRC; fellowships are from the Australian Research Council (to B.A.C.); the Leukemia and Lymphoma Society (SCOR Grants 7413 and 7001-13); and a Victorian State Government Operational Infrastructure Support Grant. The authors thank A. Strasser, B.T. Kile, and T. Mak for mice, J. Corbin for excellent technical assistance and E. Lanera and K. Scicluna for outstanding animal husbandry.