HIV 感染的巨噬细胞抵抗高效的 NK 细胞介导的杀伤，同时保留炎症细胞因子反应。
HIV-infected macrophages resist efficient NK cell-mediated killing while preserving inflammatory cytokine responses.
机构信息
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
出版信息
Cell Host Microbe. 2021 Mar 10;29(3):435-447.e9. doi: 10.1016/j.chom.2021.01.006. Epub 2021 Feb 10.
Natural killer (NK) cells are innate cytolytic effectors that target HIV-infected CD4 T cells. In conjunction with antibodies recognizing the HIV envelope, NK cells also eliminate HIV-infected targets through antibody-dependent cellular cytotoxicity (ADCC). However, how these NK cell functions impact infected macrophages is less understood. We show that HIV-infected macrophages resist NK cell-mediated killing. Compared with HIV-infected CD4 T cells, initial innate NK cell interactions with HIV-infected macrophages skew the response toward cytokine production, rather than release of cytolytic contents, causing inefficient elimination of infected macrophages. Studies with chimeric antigen receptor (CAR) T cells demonstrate that the viral envelope is equally accessible on CD4 T cells and macrophages. Nonetheless, ADCC against macrophages is muted compared with ADCC against CD4 T cells. Thus, HIV-infected macrophages employ mechanisms to evade immediate cytolytic NK cell function while preserving inflammatory cytokine responses. These findings emphasize the importance of eliminating infected macrophages for HIV cure efforts.
自然杀伤 (NK) 细胞是先天的细胞溶解效应细胞，可靶向感染 HIV 的 CD4 T 细胞。与识别 HIV 包膜的抗体结合，NK 细胞还通过抗体依赖性细胞毒性 (ADCC) 消除感染 HIV 的靶标。然而，这些 NK 细胞功能如何影响受感染的巨噬细胞尚不清楚。我们表明，感染 HIV 的巨噬细胞抵抗 NK 细胞介导的杀伤。与感染 HIV 的 CD4 T 细胞相比，初始先天 NK 细胞与感染 HIV 的巨噬细胞相互作用会使反应偏向于细胞因子的产生，而不是细胞溶解内容物的释放，从而导致对感染的巨噬细胞的清除效率降低。嵌合抗原受体 (CAR) T 细胞的研究表明，HIV 包膜在 CD4 T 细胞和巨噬细胞上同样容易接近。尽管如此，针对巨噬细胞的 ADCC 与针对 CD4 T 细胞的 ADCC 相比明显减弱。因此，感染 HIV 的巨噬细胞采用了逃避即刻细胞溶解 NK 细胞功能的机制，同时保留了炎症细胞因子反应。这些发现强调了消除感染的巨噬细胞对于 HIV 治愈努力的重要性。
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