title: Cytomegalovirus impairs antiviral CD8+ T cell immunity by recruiting inflammatory monocytes.
abstract: Inflammatory monocytes are key early responders to infection that contribute to pathogen-host interactions in diverse ways. Here, we report that the murine cytomegalovirus-encoded CC chemokine, MCK2, enhanced CCR2-dependent recruitment of these cells to modulate antiviral immunity, impairing virus-specific CD8(+) T cell expansion and differentiation into effector cytotoxic T lymphocytes, thus reducing the capacity to eliminate viral antigen-bearing cells and slowing viral clearance. Adoptive transfer of inflammatory monocytes into Ccr2(-/-)Ccl2(-/-) mice impaired virus antigen-specific clearance. Cytomegalovirus therefore enhances a natural CCR2-dependent immune regulatory network to modulate adaptive immunity via nitric oxide production, reminiscent of the monocytic subtype of myeloid-derived suppressor cells primarily implicated in cancer immunomodulation.
authors: Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors: Lisa P
authors: LP
authors: Daley-Bauer
authors: Grace M
authors: GM
authors: Wynn
authors: Edward S
authors: ES
authors: Mocarski
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019742:Chemokines, CC / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology*; D018146:Muromegalovirus / Q000276:immunology*; D009569:Nitric Oxide / Q000096:biosynthesis; D014764:Viral Proteins / Q000276:immunology
chemical_list: D018932:Chemokine CCL2; D019742:Chemokines, CC; C121663:MCK-2 protein, Mouse cytomegalovirus 1; D014764:Viral Proteins; D009569:Nitric Oxide