Neutrophils recruited by IL-22 in peripheral tissues function as TRAIL-dependent antiviral effectors against MCMV — ASN Events
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  2. Concurrent Symposia 1 Cytokines and the regulation of tissue resident immune cells
  3. Neutrophils recruited by IL-22 in peripheral tissues function as TRAIL-dependent antiviral effectors against MCMV

Neutrophils recruited by IL-22 in peripheral tissues function as TRAIL-dependent antiviral effectors against MCMV (#87)

Ian R Humphreys 1 , Maria A Stacey 1 , Morgan Marsden 1 , Tu Anh Pham 2 , Simon Clare 2 , Garry Dolton 1 , Gabrielle Stack 1 , Emma Jones 1 , Paul Klenerman 3 , Awen M Gallimore 1 , Philip R Taylor 1 , Robert J Snelgrove 4 , Trevor D Lawley 2 , Gordon Dougan 2 , Chris A Benedict 5 , Simon A Jones 1 , Gavin WG Wilkinson 1
  1. Cardiff University, Cardiff, Wales, UK
  2. Wellcome Trust Sanger Institute, Cambridgeshire, UK
  3. Oxford University, Oxford, UK
  4. Imperial College, London, UK
  5. La Jolla Institute for Allergy and Immunology, San Diego, USA

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. In particular, the role that cytokines play in the orchestration of antiviral immunity during acute infection requires a better understanding. 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). Interestingly, TRAIL-mediated control of MCMV was not associated with the induction of cell death in vitro. Collectively, 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.