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| Status |
Public on Sep 25, 2023 |
| Title |
SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-g and NK cells [BALF_NK_SARSWu_NHP] |
| Organism |
Macaca fascicularis |
| Experiment type |
Expression profiling by array
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| Summary |
SARS-CoV-2 RNA generally becomes undetectable in upper airways after a few days or weeks post-infection. It is unclear however if the virus persists in other parts of the body and which mechanism(s) regulate SARS-CoV-2 persistence. We addressed this question in the macaque model. Replication-competent virus was detected in bronchioalveolar lavages (BAL) macrophages beyond 6 months post-infection. SARS-CoV-2 propagated in BAL macrophages from cell-to-cell. IFN-γ inhibited this replication. IFN-γ production within BAL lymphocytes was strongest in NKG2r+CD8+ T and NKG2Alo NK cells and was further increased in NKG2Alo NK cells after Spike protein stimulation. However, IFN-γ production was impaired in NK cells from animals with persisting virus. IFN-γ also enhanced MHC-E expression on BAL macrophages, possibly inhibiting natural killer cell mediated killing. Animals with less persisting virus mounted adaptive NK cells escaping this MHC-E dependent inhibition. Our findings reveal an interplay between NK cells and macrophages mediated by IFN-γ, regulating SARS-CoV-2 persistence in macrophages.
Gene expression in bronchoalveolar lavage fluid (BALF) NK cells in SARS-CoV-2 convalescent monkeys.
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| Overall design |
Gene expression profiles in NKG2a/c+ NK cells from BALF of 15 wuhan infected cynomolgus macaques and 5 healthy controls at ≥461 days post-infection, based on mRNA counts normalized via the nanoString nCounter System.
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| Contributor(s) |
Huot N, Planchais C, Rosenbaum P, Contreras V, Jacquelin B, Petitdemange C, Lazzerini M, Beaumont E, Orta-Resendiz A, Rey FA, Reeves RK, Le Grand R, Mouquet H, Müller-Trutwin M |
| Citation(s) |
37919524 |
| Submission date |
Sep 21, 2023 |
| Last update date |
Dec 26, 2023 |
| Contact name |
Nicolas Huot |
| E-mail(s) |
nicolas.huot@pasteur.fr
|
| Organization name |
Institut Pasteur
|
| Street address |
28, rue du Dr Roux
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| City |
Paris |
| ZIP/Postal code |
75015 |
| Country |
France |
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| Platforms (1) |
| GPL29936 |
nCounter NHP Immunology v2 Panel [NS_NHP_Immunology_V2.0] |
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| Samples (20)
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| This SubSeries is part of SuperSeries: |
| GSE243734 |
SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-g and NK cells |
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| Relations |
| BioProject |
PRJNA1019727 |
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