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摘要
M Phi comprise a heterogeneous population of cells, which contribute to host defense and maintenance of immune homeostasis. M Phi may be infected by human cytomegalovirus ( HCMV), which has evolved different strategies to subvert the immune response. In the present study, we comparatively analyzed the natural killer (NK) cell response against HCMV (TB40E)-infected proinflammatory (M1) and antinflammatory (M2) M Phi, derived from autologous monocytes, cultured in the presence of GM-CSF and M-CSF, respectively. M1 M Phi were more resistant to infection and secreted IL-6, TNF-alpha, IFN-alpha, and IL-12; by contrast, in HCMV-infected M2 M Phi, proinflammatory cytokines, IL-10, and IFN-alpha production were limited and IL-12 was undetectable. NK cell degranulation was triggered by interaction with HCMV-infected M1 and M2 M Phi at 48 h postinfection. The response was partially inhibited by specific antiNKp46, anti-DNAM-1, and anti-2B4 mAb, thus supporting a dominant role of these activating receptors. By contrast, only HCMV-infected M1 M Phi efficiently promoted NK cell-mediated IFN-gamma secretion, an effect partially related to IL-12 production. These observations reveal differences in the NK cell response triggered by distinct, HCMV-infected, monocyte-derived cell types, which may be relevant in the immunopathology of this viral infection. J. Leukoc. Biol. 90: 717-726; 2011.
- 出版日期2011-10
