CD160 Promotes NK Cell Functions by Upregulating Glucose Metabolism and Negatively Correlates With HIV Disease Progression

Abstract

Natural killer (NK) cells are crucial for immune responses to viral infections. CD160 is an important NK cell activating receptor, with unknown function in HIV infection. Here, we found that CD160 expression was reduced on NK cells from HIV-infected individuals and its expression was negatively correlated with HIV disease progression. Further, GLUT1 expression and glucose uptake were higher in CD160+ NK cells, and the results of RNA-seq and flow cytometry demonstrated that CD160 positively regulated glucose metabolism through the PI3K/AKT/mTOR/s6k signaling pathway, thereby enhancing NK cell function. Moreover, we determined that reduced CD160 expression on NK cells could be attributed to the higher plasma levels of TGF-β1 in HIV-infected individuals. Overall, these results highlight the vital role of CD160 in HIV disease progression and regulation of glucose metabolism, indicating a potential target for HIV immunotherapy.

HIV-differentiated metabolite N-Acetyl-L-Alanine dysregulates human natural killer cell responses toMycobacterium tuberculosisinfection

“…NK cells have been reported to use glycolysis and oxidative phosphorylation (Oxphos) pathways to provide energy for various physiological activities, such as activation and proliferation[47, 48]. We found that the glycolysis of □ Mtb -activated NKcells is significantly reduced, and this may explain the decline of IFN-□ production due to the growing consensus that glycolysis is critical for IFN- production by NK cells [49].…”

HIV-Differentiated Metabolite N-Acetyl-L-Alanine Dysregulates Human Natural Killer Cell Responses to Mycobacterium tuberculosis Infection

“…NK cells have been reported to use glycolysis and oxidative phosphorylation (Oxphos) pathways to provide energy for various physiological activities, such as activation and proliferation [ 46 , 47 ]. We found that the glycolysis of γ Mtb -activated NK cells was significantly reduced, and this may explain the decline in IFN-γ production due to the growing consensus that glycolysis is critical for IFN-γ production by NK cells [ 48 ].…”

CD160 receptor in CLL: Current state and future avenues

“…Moreover, CD160 is also implicated in the regulation of NK-cell metabolism. It was reported that CD160 expression is positively correlated with the expression of the glucose transporter (GLUT1) and glucose uptake in NK cells, which is indispensable for NK-cell functioning and IFN-γ secretion ( 14 , 78 ). CD160 expression in NK cells upregulates glucose metabolism through the activation of the AKT/mTOR/s6k signaling pathway ( 14 ).…”

“…It was reported that CD160 expression is positively correlated with the expression of the glucose transporter (GLUT1) and glucose uptake in NK cells, which is indispensable for NK-cell functioning and IFN-γ secretion ( 14 , 78 ). CD160 expression in NK cells upregulates glucose metabolism through the activation of the AKT/mTOR/s6k signaling pathway ( 14 ). In addition, mTORC1 signaling was previously demonstrated to be required for the upregulation of GLUT1 expression and the expression of glycolysis rate-limiting enzymes such hexokinase 2 and lactate dehydrogenase A, which enhance glucose uptake and glycolysis and increase NK-cell functioning ( 79 ).…”

“…This exhausted phenotype is due to the expression of TGF-β by tumor cells and inhibits NK-cell functions ( 87 ). Similarly, the elevated levels of TGF-β1 in human immunodeficiency virus (HIV)-infected individuals decrease the expression of CD160 in NK cells and enhance HIV disease progression ( 14 ). This downregulation may be mediated through the upregulation of specific miRNAs that inhibit CD160 transcription by TGF-β1 ( 14 ).…”