IL-15 reprogramming compensates for NK cell mitochondrial dysfunction in HIV-1 infection
Dynamic regulation of cellular metabolism is important for maintaining homeostasis and can directly influence immune cell function and differentiation, including NK cell responses. Persistent HIV-1 infection leads to a state of chronic immune activation, NK cell subset redistribution, and progressive NK cell dysregulation. In this study, we examined the metabolic processes that characterize NK cell subsets in HIV-1 infection, including adaptive NK cell subpopulations expressing the activating receptor NKG2C, which expand during chronic infection. These adaptive NK cells exhibit an enhanced metabolic profile in HIV-1- individuals infected with human cytomegalovirus (HCMV). However, the bioenergetic advantage of adaptive CD57+NKG2C+ NK cells is diminished during chronic HIV-1 infection, where NK cells uniformly display reduced oxidative phosphorylation (OXPHOS). Defective OXPHOS was accompanied by increased mitochondrial depolarization, structural alterations, and increased DRP-1 levels promoting fission, suggesting that mitochondrial defects are restricting the metabolic plasticity of NK cell subsets in HIV-1 infection. The metabolic requirement for the NK cell response to receptor stimulation was alleviated upon IL-15 pretreatment, which enhanced mammalian target of rapamycin complex 1 (mTORC1) activity. IL-15 priming enhanced NK cell functionality to anti-CD16 stimulation in HIV-1 infection, representing an effective strategy for pharmacologically boosting NK cell responses.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
JCI insight - 9(2024), 4 vom: 16. Jan. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Moreno-Cubero, Elia [VerfasserIn] |
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| Links: |
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| Themen: |
AIDS/HIV |
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| Anmerkungen: |
Date Completed 23.02.2024 Date Revised 13.03.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1172/jci.insight.173099 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM368757528 |
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| 520 | |a Dynamic regulation of cellular metabolism is important for maintaining homeostasis and can directly influence immune cell function and differentiation, including NK cell responses. Persistent HIV-1 infection leads to a state of chronic immune activation, NK cell subset redistribution, and progressive NK cell dysregulation. In this study, we examined the metabolic processes that characterize NK cell subsets in HIV-1 infection, including adaptive NK cell subpopulations expressing the activating receptor NKG2C, which expand during chronic infection. These adaptive NK cells exhibit an enhanced metabolic profile in HIV-1- individuals infected with human cytomegalovirus (HCMV). However, the bioenergetic advantage of adaptive CD57+NKG2C+ NK cells is diminished during chronic HIV-1 infection, where NK cells uniformly display reduced oxidative phosphorylation (OXPHOS). Defective OXPHOS was accompanied by increased mitochondrial depolarization, structural alterations, and increased DRP-1 levels promoting fission, suggesting that mitochondrial defects are restricting the metabolic plasticity of NK cell subsets in HIV-1 infection. The metabolic requirement for the NK cell response to receptor stimulation was alleviated upon IL-15 pretreatment, which enhanced mammalian target of rapamycin complex 1 (mTORC1) activity. IL-15 priming enhanced NK cell functionality to anti-CD16 stimulation in HIV-1 infection, representing an effective strategy for pharmacologically boosting NK cell responses | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a AIDS/HIV | |
| 650 | 4 | |a Immunology | |
| 650 | 4 | |a Mitochondria | |
| 650 | 4 | |a NK cells | |
| 650 | 7 | |a Interleukin-15 |2 NLM | |
| 700 | 1 | |a Alrubayyi, Aljawharah |e verfasserin |4 aut | |
| 700 | 1 | |a Balint, Stefan |e verfasserin |4 aut | |
| 700 | 1 | |a Ogbe, Ane |e verfasserin |4 aut | |
| 700 | 1 | |a Gill, Upkar S |e verfasserin |4 aut | |
| 700 | 1 | |a Matthews, Rebecca |e verfasserin |4 aut | |
| 700 | 1 | |a Kinloch, Sabine |e verfasserin |4 aut | |
| 700 | 1 | |a Burns, Fiona |e verfasserin |4 aut | |
| 700 | 1 | |a Rowland-Jones, Sarah L |e verfasserin |4 aut | |
| 700 | 1 | |a Borrow, Persephone |e verfasserin |4 aut | |
| 700 | 1 | |a Schurich, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Dustin, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Peppa, Dimitra |e verfasserin |4 aut | |
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