How HIV-1 shapes the interplay between macrophages and NK cells

HIV-1-infected macrophages upregulate activating surface molecules such as IL-15Rα, CD48, and NKG2D ligands, thereby enhancing proinflammatory cytokine production by NK cells. However, this does not translate into strong cytotoxic activation. NK cells from people living with HIV (PLWH) on therapy remain responsive to priming by activated macrophages—especially subsets expressing inhibitory HLA receptors such as KIR or NKG2A. In contrast, the HIV-1-associated CD56 negative NK cells remain functionally impaired. These findings help explain the limited antiviral efficacy of NK cells during HIV-1 infection and support the development of improved "shock and kill" approaches targeting the viral reservoir. 

The results of the study were published in iScience and can be found here.

Image: Natural killer cell (source: NIAID via https://commons.wikimedia.org/wiki/File:Human_Natural_Killer_Cell_-_51630111330.jpg; Creative Commons Attribution 2.0).