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

• Type of Material: Article
• Authors: Nicolas Huot, Institut Pasteur, Unité HIV, France; Philippe Rascle, Institut Pasteur, Unité HIV, France; Caroline Petitdemange, Institut Pasteur, Unité HIV, France; Vanessa Contreras, Université Paris Sud-Inserm; Christina M Stuerzel, Ulm University; Eduard Baquero, Institut Pasteur, Unité HIV, France; Justin L Harper, Emory University; Caroline Passaes, Institut Pasteur, Unité HIV, France; Rachel Legendre, Institut Pasteur, Unité HIV, France; Hugo Varet, Institut Pasteur, Unité HIV, France; Yoann Madec, Institut Pasteur, Unité HIV, France; Ulrike Sauermann, Deutsches Primatenzentrum - Leibniz Institut für Primatenforschung; Christiane Stahl-Hennig, Deutsches Primatenzentrum - Leibniz Institut für Primatenforschung; Jacob Nattermann, Universitätsklinikum Bonn, Germany; Asier Saez-Cirion, Institut Pasteur, Unité HIV, France; Roger Le Grand, Université Paris Sud-Inserm; Keith R Reeves, Harvard Medical School; Mirko Paiardini, Emory University; Frank Kirchhoff, 4Ulm University Medical Center; Beatrice Jacquelin, Institut Pasteur, Unité HIV, France; Michaela Mueller-Trutwin, Institut Pasteur, Unité HIV, France
• Language: English
• Date: 2021-02-24
• Publisher: NATURE PORTFOLIO
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-021-21402-1
• Title of Journal or Parent Work: NATURE COMMUNICATIONS
• Volume: 12
• Issue: 1
• Start Page: 1282
• End Page: 1282
• Grant/Funding Information: We gratefully acknowledge the support to IDMIT from the French government: Investments for the Future program for infrastructures (PIA) through the ANR-11-INBS-0008 grant as well as from the PIA grant ANR-10-EQPX-02-01 to the FlowCyTech facility at IDMIT. We equally acknowledge the Investments for Future grant ANR-10–INSB–04 to support the UtechS Photonic BioImaging (Imagopole) and C2RT facilities at Institut Pasteur.; The Biomics Platform (C2RT, Institut Pasteur) is supported by France Génomique (ANR-10-INBS-09-09) and IBISA NH was supported by the VRI Labex, the Fondation Jacquelin Beytout and Institut Pasteur, and PR was recipient of a PhD fellowship from the University Paris Diderot, Sorbonne Paris Cité. C.P. was supported by a MSDAvenir Postdoctoral Fellowship Grant. FK was supported by the DFG (CRC 1279 and SPP 1923. We would like to acknowledge grant support from ANRS, the Fondation Jacqueline Beytout, and the Fondation Les Ailes to M.M.T., from the NIH (R01AI143457) to M.M.T. and R.K.R. and from MSDAvenir to A.S.C. and M.M.T.; J.L.H. and M.P. were supported by NIH grant R01AI116379 to M.P. and by ORIP/OD award P51OD011132 to Yerkes National Primate Research Center. J.N. was supported by the DFG (SPP 1937, SFB TR57), the Hector Foundation, and the DZIF (TTU-HIV)
• Keywords: HLA-E; SURFACE EXPRESSION; Multidisciplinary Sciences; NATURAL-KILLER-CELLS; VIRAL REPLICATION; IFN-GAMMA; SIGNAL PEPTIDE; EPIGENETIC REGULATION; AFRICAN-GREEN MONKEYS; HIV; Science & Technology - Other Topics; INFECTION; Science & Technology
• Research Categories: Biology, Biostatistics; Health Sciences, Public Health; Health Sciences, General

Abstract

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 NKG2alow 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.