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Neutrophils recruited by IL-22 in peripheral tissues function as TRAIL-dependent antiviral effectors against MCMV

Stacey, Maria A., Marsden, Morgan, Pham N, Tu Anh, Clare, Simon, Dolton, Garry Michael, Stack, Gabrielle, Jones, Emma, Klenerman, Paul, Gallimore, Awen Myfanwy, Taylor, Philip Russel, Snelgrove, Robert J., Lawley, Trevor D., Dougan, Gordon, Benedict, Chris A., Jones, Simon Arnett, Wilkinson, Gavin William Grahame and Humphreys, Ian R. 2014. Neutrophils recruited by IL-22 in peripheral tissues function as TRAIL-dependent antiviral effectors against MCMV. Cell Host & Microbe 15 (4) , pp. 471-483. 10.1016/j.chom.2014.03.003

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Abstract

During primary infection, murine cytomegalovirus (MCMV) spreads systemically, resulting in virus replication and pathology in multiple organs. This disseminated infection is ultimately controlled, but the underlying immune defense mechanisms are unclear. Investigating the role of the cytokine IL-22 in MCMV infection, we discovered an unanticipated function for neutrophils as potent antiviral effector cells that restrict viral replication and associated pathogenesis in peripheral organs. NK-, NKT-, and T cell-secreted IL-22 orchestrated antiviral neutrophil-mediated responses via induction in stromal nonhematopoietic tissue of the neutrophil-recruiting chemokine CXCL1. The antiviral effector properties of infiltrating neutrophils were directly linked to the expression of TNF-related apoptosis-inducing ligand (TRAIL). Our data identify a role for neutrophils in antiviral defense, and establish a functional link between IL-22 and the control of antiviral neutrophil responses that prevents pathogenic herpesvirus infection in peripheral organs.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Publisher: Cell Press
ISSN: 1931-3128
Funders: Wellcome Trust
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 4 March 2014
Last Modified: 05 Feb 2019 15:59
URI: http://orca.cf.ac.uk/id/eprint/60454

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