HIV-1 infection of macrophages differentially primes NK-cell cytotoxicity and proinflammatory cytokine production

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...

Full description

Saved in:
Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:iScience
Subjects:
Immunology
Immune response
Virology
Online Access:http://www.sciencedirect.com/science/article/pii/S258900422501140X
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2589-0042

Similar Items