Immunology Unit, Pompeu Fabra University, Barcelona, Spain.
J Leukoc Biol. 2011 Oct;90(4):717-26. doi: 10.1189/jlb.0311171. Epub 2011 Jul 8.
MΦ comprise a heterogeneous population of cells, which contribute to host defense and maintenance of immune homeostasis. MΦ 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) MΦ, derived from autologous monocytes, cultured in the presence of GM-CSF and M-CSF, respectively. M1 MΦ were more resistant to infection and secreted IL-6, TNF-α, IFN-α, and IL-12; by contrast, in HCMV-infected M2 MΦ, proinflammatory cytokines, IL-10, and IFN-α production were limited and IL-12 was undetectable. NK cell degranulation was triggered by interaction with HCMV-infected M1 and M2 MΦ at 48 h postinfection. The response was partially inhibited by specific anti-NKp46, anti-DNAM-1, and anti-2B4 mAb, thus supporting a dominant role of these activating receptors. By contrast, only HCMV-infected M1 MΦ efficiently promoted NK cell-mediated IFN-γ 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.
MΦ 是一个异质性的细胞群体，它们有助于宿主防御和维持免疫稳态。MΦ 可能会被人类巨细胞病毒（HCMV）感染，HCMV 已经进化出不同的策略来颠覆免疫反应。在本研究中，我们比较分析了针对 HCMV（TB40E）感染的促炎（M1）和抗炎（M2）MΦ 的自然杀伤（NK）细胞反应，这些 MΦ 是从自体单核细胞分化而来的，分别在 GM-CSF 和 M-CSF 的存在下培养。M1 MΦ 对感染的抵抗力更强，并分泌 IL-6、TNF-α、IFN-α 和 IL-12；相比之下，在 HCMV 感染的 M2 MΦ 中，促炎细胞因子、IL-10 和 IFN-α 的产生受到限制，IL-12 无法检测到。NK 细胞脱颗粒是通过与感染 HCMV 的 M1 和 M2 MΦ 在感染后 48 小时的相互作用触发的。该反应被特异性抗 NKp46、抗 DNAM-1 和抗 2B4 mAb 部分抑制，因此支持这些激活受体的主导作用。相比之下，只有感染 HCMV 的 M1 MΦ 能够有效地促进 NK 细胞介导的 IFN-γ 分泌，这种作用部分与 IL-12 的产生有关。这些观察结果揭示了不同的、感染 HCMV 的单核细胞衍生细胞类型触发的 NK 细胞反应的差异，这在这种病毒感染的免疫病理学中可能是相关的。
