Mitochondrial dysfunction contributes to impaired cytokine production of CD56 bright NK cells from HIV(+) individuals under effective antiviral therapy

HIV infection is associated with impaired NK cell activity, which is only incompletely restored under antiretroviral therapy. Analysing the bioenergetics profiles of oxygen consumption, we observed several parameters were significantly reduced in HIV(+) NK cells, indicating a mitochondrial defect. A...

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Bibliographic Details
Published inThe Journal of infectious diseases
Main Authors ToVinh, Michael, Hörr, Gregor, Dobrikova, Kristiyana, Gotter, Christina, Rommel, Clemens, Hoffmeister, Christoph, Raabe, Jan, Kaiser, Kim M, Finnemann, Claudia, Bischoff, Jenny, Rieke, Gereon J, Wilhelm, Christoph, Schmitt, Vanessa, Möhl, Christoph, Aghabeig, Mansoureh, Schwarze-Zander, Carolynne, Boesecke, Christoph, van Bremen, Kathrin, Wasmuth, Jan-Christian, Strassburg, Christian P, Rockstroh, Jürgen K, Spengler, Ulrich, Krämer, Benjamin, Nattermann, Jacob
Format Journal Article
LanguageEnglish
Published United States 21.03.2022
Subjects
IFNγ
HIV
immunometabolism
NK cell
mitochondrial dysfunction
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Summary:HIV infection is associated with impaired NK cell activity, which is only incompletely restored under antiretroviral therapy. Analysing the bioenergetics profiles of oxygen consumption, we observed several parameters were significantly reduced in HIV(+) NK cells, indicating a mitochondrial defect. Accordingly, we found HIV(+) CD56 bright NK cells to display a decreased mitochondrial membrane potential and mitochondrial mass. Both parameters were positively correlated with IFNγ production of NK cells. Finally, we demonstrated that stimulation of HIV(+) NK cells with MitoTEMPO, mitochondria-targeting antioxidant, significantly improved IFNγ production. In conclusion, we identified mitochondrial dysfunction as a mechanism that contributes to impaired NK cell function.
ISSN:1537-6613