tetano
Editor, Senior Moderator
Nat Immunol
. 2023 Nov 2.
doi: 10.1038/s41590-023-01661-4. Online ahead of print. SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells
Nicolas Huot[SUP] 1 [/SUP], Cyril Planchais[SUP] 2 [/SUP], Pierre Rosenbaum[SUP] 2 [/SUP], Vanessa Contreras[SUP] 3 [/SUP], Beatrice Jacquelin[SUP] 4 [/SUP], Caroline Petitdemange[SUP] 4 [/SUP], Marie Lazzerini[SUP] 4 [/SUP], Emma Beaumont[SUP] 4 [/SUP], Aurelio Orta-Resendiz[SUP] 4 [/SUP], Félix A Rey[SUP] 5 [/SUP], R Keith Reeves[SUP] 6 7 8 9 [/SUP], Roger Le Grand[SUP] 3 [/SUP], Hugo Mouquet[SUP] 2 [/SUP], Michaela Müller-Trutwin[SUP] 4 [/SUP]
Affiliations
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[SUP]+[/SUP]CD8[SUP]+[/SUP] T cells and NKG2A[SUP]lo[/SUP] natural killer (NK) cells and was further increased in NKG2A[SUP]lo[/SUP] 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.
. 2023 Nov 2.
doi: 10.1038/s41590-023-01661-4. Online ahead of print. SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells
Nicolas Huot[SUP] 1 [/SUP], Cyril Planchais[SUP] 2 [/SUP], Pierre Rosenbaum[SUP] 2 [/SUP], Vanessa Contreras[SUP] 3 [/SUP], Beatrice Jacquelin[SUP] 4 [/SUP], Caroline Petitdemange[SUP] 4 [/SUP], Marie Lazzerini[SUP] 4 [/SUP], Emma Beaumont[SUP] 4 [/SUP], Aurelio Orta-Resendiz[SUP] 4 [/SUP], Félix A Rey[SUP] 5 [/SUP], R Keith Reeves[SUP] 6 7 8 9 [/SUP], Roger Le Grand[SUP] 3 [/SUP], Hugo Mouquet[SUP] 2 [/SUP], Michaela Müller-Trutwin[SUP] 4 [/SUP]
Affiliations
- PMID: 37919524
- DOI: 10.1038/s41590-023-01661-4
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[SUP]+[/SUP]CD8[SUP]+[/SUP] T cells and NKG2A[SUP]lo[/SUP] natural killer (NK) cells and was further increased in NKG2A[SUP]lo[/SUP] 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.