Cytomegalovirus Impairs Antiviral CD8+ T Cell Immunity by Recruiting Inflammatory Monocytes

• Published in: Immunity (Cambridge, Mass.) Vol. 37; no. 1; pp. 122 - 133
• Main Authors: Daley-Bauer, Lisa P., Wynn, Grace M., Mocarski, Edward S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.07.2012; Elsevier Limited
• Subjects: Animals; CD8-Positive T-Lymphocytes - immunology; Cell Line; Chemokine CCL2 - genetics; Chemokine CCL2 - immunology; Chemokine CCL2 - metabolism; Chemokines; Chemokines, CC - immunology; Cytomegalovirus; Drinking water; Flow cytometry; Herpesviridae Infections - immunology; Immune system; Infections; Mice; Mice, Inbred C57BL; Mice, Knockout; Monocytes - immunology; Muromegalovirus - immunology; Nitric Oxide - biosynthesis; Viral infections; Viral Proteins - immunology
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2012.04.014

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. [Display omitted] ► Viral chemokine enhances inflammatory monocyte recruitment from bone marrow ► Recruitment depends upon host CCR2 signaling ► Recruitment impairs the antigen-specific CD8+ T cell immunity ► Recruitment facilitates viral persistence