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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.

SUBMITTER: Daley-Bauer LP

PROVIDER: S-EPMC3412053 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Cytomegalovirus impairs antiviral CD8+ T cell immunity by recruiting inflammatory monocytes.

Daley-Bauer Lisa P LP Wynn Grace M GM Mocarski Edward S ES

Immunity 20120701 1

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 tra ...[more]

PMID: 22840843

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