[PDF][PDF] HIV-infected macrophages resist efficient NK cell-mediated killing while preserving inflammatory cytokine responses

KL Clayton, G Mylvaganam, A Villasmil-Ocando… - Cell host & …, 2021 - cell.com
KL Clayton, G Mylvaganam, A Villasmil-Ocando, H Stuart, MV Maus, M Rashidian
Cell host & microbe, 2021cell.com
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 …
Summary
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.
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