Details

Autor(en) / Beteiligte

• Stacey, Maria A.
• Marsden, Morgan
• Pham N, Tu Anh
• Clare, Simon
• Dolton, Garry
• Stack, Gabrielle
• Jones, Emma
• Klenerman, Paul
• Gallimore, Awen M.
• Taylor, Philip R.
• Snelgrove, Robert J.
• Lawley, Trevor D.
• Dougan, Gordon
• Benedict, Chris A.
• Jones, Simon A.
• Wilkinson, Gavin W.G.
• Humphreys, Ian R.

Titel

Neutrophils Recruited by IL-22 in Peripheral Tissues Function as TRAIL-Dependent Antiviral Effectors against MCMV

Ist Teil von

• Cell host & microbe, 2014-04, Vol.15 (4), p.471-483

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

ScienceDirect

Beschreibungen/Notizen

• 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. [Display omitted] •Neutrophils are critical antiviral effector cells during MCMV virus infection•Neutrophils directly inhibit virus replication in a TRAIL-dependent manner•IL-22 inhibits virus replication in peripheral but not secondary lymphoid tissues•IL-22 orchestrates CXCL1-dependent neutrophil recruitment Murine cytomegalovirus (MCMV) targets multiple peripheral organs during infection. Stacey et al. report that in response to MCMV infection, NK, NKT, and T cells secrete the cytokine IL-22, which recruits antiviral neutrophils to infected peripheral organs in a CXCL1-dependent manner. Neutrophils exert antiviral effector functions via proapoptotic TRAIL expression.