HIV-1 infection of macrophages differentially primes NK-cell cytotoxicity and proinflammatory cytokine production
Summary: Natural killer (NK) cells are innate cytotoxic lymphocytes with antiviral functions explored in “shock and kill” strategies to eliminate the HIV-1 reservoir. For optimal activity against infected targets, NK cells require priming. This study examined how macrophages prime NK cells following...
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| Language: | English |
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Elsevier
2025-07-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422501140X |
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| author | Leonore Mensching Maya Beiersdorfer Sebastian Schloer Sandra Köllmann Friederike Reinsberg Benedetta Padoan Pia Fittje Timo Trenkner Annika Zaayenga Gloria Martrus Maher Almahfoud Christina M. Stürzel Daniel Sauter Frank Kirchhoff Julian Schulze zur Wiesch Marcus Altfeld Wilfredo F. Garcia-Beltran Angelique Hoelzemer |
| author_facet | Leonore Mensching Maya Beiersdorfer Sebastian Schloer Sandra Köllmann Friederike Reinsberg Benedetta Padoan Pia Fittje Timo Trenkner Annika Zaayenga Gloria Martrus Maher Almahfoud Christina M. Stürzel Daniel Sauter Frank Kirchhoff Julian Schulze zur Wiesch Marcus Altfeld Wilfredo F. Garcia-Beltran Angelique Hoelzemer |
| author_sort | Leonore Mensching |
| collection | DOAJ |
| description | Summary: Natural killer (NK) cells are innate cytotoxic lymphocytes with antiviral functions explored in “shock and kill” strategies to eliminate the HIV-1 reservoir. For optimal activity against infected targets, NK cells require priming. This study examined how macrophages prime NK cells following HIV-1 infection. We found that HIV-1-infected monocyte-derived macrophages upregulated membrane-bound IL-15Rα, NKG2D ligands, CD48, and IL-18. While crosstalk between NK cells and infected macrophages enhanced proinflammatory cytokine production, it led to only weak priming of NK-cell cytotoxicity. In people living with HIV-1 (PLWH) on antiretroviral therapy, macrophage priming remained intact and polyfunctional, with the strongest response in CD56dim KIR+ and/or NKG2A+ NK cells. However, CD56neg NK cells —a subset unique to HIV-1 infection— remained dysfunctional. These findings elucidate how HIV-1 alters macrophage-NK cell crosstalk and underscore the need for therapeutic strategies that enhance NK-cell cytotoxicity in efforts toward a functional HIV-1 cure. |
| format | Article |
| id | doaj-art-3dae15ae49ca4d0e87de972d9e1f6826 |
| institution | OA Journals |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-3dae15ae49ca4d0e87de972d9e1f68262025-08-20T02:35:00ZengElsevieriScience2589-00422025-07-0128711287910.1016/j.isci.2025.112879HIV-1 infection of macrophages differentially primes NK-cell cytotoxicity and proinflammatory cytokine productionLeonore Mensching0Maya Beiersdorfer1Sebastian Schloer2Sandra Köllmann3Friederike Reinsberg4Benedetta Padoan5Pia Fittje6Timo Trenkner7Annika Zaayenga8Gloria Martrus9Maher Almahfoud10Christina M. Stürzel11Daniel Sauter12Frank Kirchhoff13Julian Schulze zur Wiesch14Marcus Altfeld15Wilfredo F. Garcia-Beltran16Angelique Hoelzemer17Department of Medicine, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; Research Department of Virus Immunology, Leibniz Institute of Virology, Hamburg, GermanyDepartment of Medicine, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, GermanyInstitute of Immunology, Research Group Immunopharmacology, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, GermanyDepartment of Medicine, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; Research Department of Virus Immunology, Leibniz Institute of Virology, Hamburg, GermanyDepartment of Medicine, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; Research Department of Virus Immunology, Leibniz Institute of Virology, Hamburg, Germany; German Center for Infection Research (DZIF), Site Hamburg-Lübeck-Borstel-Riems, Borstel, GermanyResearch Department of Virus Immunology, Leibniz Institute of Virology, Hamburg, GermanyResearch Department of Virus Immunology, Leibniz Institute of Virology, Hamburg, GermanyDepartment of Medicine, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, GermanyDepartment of Medicine, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, GermanyResearch Department of Virus Immunology, Leibniz Institute of Virology, Hamburg, GermanyDepartment of Medicine, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, GermanyInstitute of Molecular Virology, University Medical Center, Ulm, GermanyInstitute for Medical Virology and Epidemiology of Viral Diseases, Eberhard Karls University Tübingen, Tübingen, GermanyInstitute of Molecular Virology, University Medical Center, Ulm, GermanyDepartment of Medicine, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; German Center for Infection Research (DZIF), Site Hamburg-Lübeck-Borstel-Riems, Borstel, GermanyResearch Department of Virus Immunology, Leibniz Institute of Virology, Hamburg, GermanyRagon Institute of Massachusetts General Hospital, MIT and Harvard, Cambridge, MA, USA; Department of Pathology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USADepartment of Medicine, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; Research Department of Virus Immunology, Leibniz Institute of Virology, Hamburg, Germany; German Center for Infection Research (DZIF), Site Hamburg-Lübeck-Borstel-Riems, Borstel, Germany; Institute for Infection and Vaccine Development (IIRVD), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; Corresponding authorSummary: Natural killer (NK) cells are innate cytotoxic lymphocytes with antiviral functions explored in “shock and kill” strategies to eliminate the HIV-1 reservoir. For optimal activity against infected targets, NK cells require priming. This study examined how macrophages prime NK cells following HIV-1 infection. We found that HIV-1-infected monocyte-derived macrophages upregulated membrane-bound IL-15Rα, NKG2D ligands, CD48, and IL-18. While crosstalk between NK cells and infected macrophages enhanced proinflammatory cytokine production, it led to only weak priming of NK-cell cytotoxicity. In people living with HIV-1 (PLWH) on antiretroviral therapy, macrophage priming remained intact and polyfunctional, with the strongest response in CD56dim KIR+ and/or NKG2A+ NK cells. However, CD56neg NK cells —a subset unique to HIV-1 infection— remained dysfunctional. These findings elucidate how HIV-1 alters macrophage-NK cell crosstalk and underscore the need for therapeutic strategies that enhance NK-cell cytotoxicity in efforts toward a functional HIV-1 cure.http://www.sciencedirect.com/science/article/pii/S258900422501140XImmunologyImmune responseVirology |
| spellingShingle | Leonore Mensching Maya Beiersdorfer Sebastian Schloer Sandra Köllmann Friederike Reinsberg Benedetta Padoan Pia Fittje Timo Trenkner Annika Zaayenga Gloria Martrus Maher Almahfoud Christina M. Stürzel Daniel Sauter Frank Kirchhoff Julian Schulze zur Wiesch Marcus Altfeld Wilfredo F. Garcia-Beltran Angelique Hoelzemer HIV-1 infection of macrophages differentially primes NK-cell cytotoxicity and proinflammatory cytokine production iScience Immunology Immune response Virology |
| title | HIV-1 infection of macrophages differentially primes NK-cell cytotoxicity and proinflammatory cytokine production |
| title_full | HIV-1 infection of macrophages differentially primes NK-cell cytotoxicity and proinflammatory cytokine production |
| title_fullStr | HIV-1 infection of macrophages differentially primes NK-cell cytotoxicity and proinflammatory cytokine production |
| title_full_unstemmed | HIV-1 infection of macrophages differentially primes NK-cell cytotoxicity and proinflammatory cytokine production |
| title_short | HIV-1 infection of macrophages differentially primes NK-cell cytotoxicity and proinflammatory cytokine production |
| title_sort | hiv 1 infection of macrophages differentially primes nk cell cytotoxicity and proinflammatory cytokine production |
| topic | Immunology Immune response Virology |
| url | http://www.sciencedirect.com/science/article/pii/S258900422501140X |
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