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Article Dans Une Revue Nature Immunology Année : 2023

SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells

Félix Rey
Hugo Mouquet

Résumé

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA generally becomes undetectable in upper airways after a few days or weeks postinfection. Here we used a model of viral infection in macaques to address whether SARS-CoV-2 persists in the body and which mechanisms regulate its persistence. Replication-competent virus was detected in bronchioalveolar lavage (BAL) macrophages beyond 6 months postinfection. Viral propagation in BAL macrophages occurred from cell to cell and was inhibited by interferon-γ (IFN-γ). IFN-γ production was strongest in BAL NKG2r + CD8 + T cells and NKG2A lo natural killer (NK) cells and was further increased in NKG2A lo NK cells after spike protein stimulation. However, IFN-γ production was impaired in NK cells from macaques with persisting virus. Moreover, IFN-γ also enhanced the expression of major histocompatibility complex (MHC)-E on BAL macrophages, possibly inhibiting NK cell-mediated killing. Macaques with less persisting virus mounted adaptive NK cells that escaped the MHC-E-dependent inhibition. Our findings reveal an interplay between NK cells and macrophages that regulated SARS-CoV-2 persistence in macrophages and was mediated by IFN-γ.
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hal-04597995 , version 1 (05-06-2024)

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Nicolas Huot, Cyril Planchais, Pierre Rosenbaum, Vanessa Contreras, Beatrice Jacquelin, et al.. SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells. Nature Immunology, 2023, 24 (12), pp.2068-2079. ⟨10.1038/s41590-023-01661-4⟩. ⟨hal-04597995⟩
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