SIV-induced terminally differentiated adaptive NK cells in lymph nodes associated with enhanced MHC-E restricted activity

Nicolas Huot (1) , Philippe Rascle (1) , Caroline Petitdemange (1) , Vanessa Contreras (2) , Christina M Stürzel (3) , Eduard Baquero (4) , Justin L Harper (5) , Caroline Passaes (1) , Rachel Legendre (6, 7) , Hugo Varet (6, 7) , Yoann Madec (8) , Ulrike Sauermann (9) , Christiane Stahl-Hennig (9) , Jacob Nattermann (10) , Asier Sáez-Cirión (1) , Roger Le Grand (11) , R. Keith Reeves (12) , Mirko Paiardini (5, 13) , Frank Kirchhoff (3) , Beatrice Jacquelin (1) , Michaela Müller-Trutwin (1)

1 HIV, Inflammation et persistance - HIV, Inflammation and Persistence
2 IMVA-HB - Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes
3 UUlm - University of Ulm
4 Virologie Structurale - Structural Virology
5 Yerkes National Primate Research Center [Lawrenceville, GA]
6 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB
7 C2RT - Pôle Biomics
8 Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology
9 GPC - DPZ - German Primate Center - Deutsches Primatenzentrum -- Leibniz Insitute for Primate Research -- [Göttingen, Allemagne]
10 UKB - Universitätsklinikum Bonn
11 IMVA - U1184 - Immunologie des Maladies Virales et Autoimmunes
12 HMS - Harvard Medical School [Boston]
13 Emory University School of Medicine

Natural killer (NK) cells play a critical understudied role during HIV infection in tissues. In a natural host of SIV, the African green monkey (AGM), NK cells mediate a strong control of SIVagm infection in secondary lymphoid tissues. We demonstrate that SIVagm infection induces the expansion of terminally differentiated NKG2a low NK cells in secondary lymphoid organs displaying an adaptive transcriptional profile and increased MHC-E-restricted cytotoxicity in response to SIV Env peptides while expressing little IFN-γ. Such NK cell differentiation was lacking in SIVmac-infected macaques. Adaptive NK cells displayed no increased NKG2C expression. This study reveals a previously unknown profile of NK cell adaptation to a viral infection, thus accelerating strategies toward NK-cell directed therapies and viral control in tissues.

Domains: Life Sciences [q-bio]

Nicolas Huot, Philippe Rascle, Caroline Petitdemange, Vanessa Contreras, Christina M Stürzel, et al.. SIV-induced terminally differentiated adaptive NK cells in lymph nodes associated with enhanced MHC-E restricted activity. Nature Communications, 2021, 12 (1), pp.1282. ⟨10.1038/s41467-021-21402-1⟩. ⟨pasteur-03162805⟩