1. SIV-induced terminally differentiated adaptive NK cells in lymph nodes associated with enhanced MHC-E restricted activity
- Author
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Huot, Nicolas, Rascle, Philippe, Petitdemange, Caroline, Contreras, Vanessa, Stürzel, Christina M., Baquero, Eduard, Harper, Justin L., Passaes, Caroline, Legendre, Rachel, Varet, Hugo, Madec, Yoann, Sauermann, Ulrike, Stahl-Hennig, Christiane, Nattermann, Jacob, Saez-Cirion, Asier, Le Grand, Roger, Keith Reeves, R., Paiardini, Mirko, Kirchhoff, Frank, Jacquelin, Beatrice, Müller-Trutwin, Michaela, Varet, Hugo, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Infrastructures - Infrastructure nationale pour la modélisation des maladies infectieuses humaines - - IDMIT2011 - ANR-11-INBS-0008 - INBS - VALID, Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID, HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University of Ulm (UUlm), Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Yerkes National Primate Research Center [Lawrenceville, GA], Emory University [Atlanta, GA], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Pôle Biomics (C2RT), Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (C2RT), Institut Pasteur [Paris] (IP)-Institut Pasteur [Paris] (IP), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), German Primate Center - Deutsches Primatenzentrum -- Leibniz Insitute for Primate Research -- [Göttingen, Allemagne] (GPC - DPZ), Universitätsklinikum Bonn (UKB), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Harvard Medical School [Boston] (HMS), Emory University School of Medicine, 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). 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., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), HIV, Inflammation et persistance, Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Institut Pasteur [Paris], Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
- Subjects
CD4-Positive T-Lymphocytes ,Male ,MESH: Killer Cells, Natural ,MESH: Cell Differentiation ,Lymphoid Tissue ,Science ,animal diseases ,[SDV]Life Sciences [q-bio] ,MESH: Simian Immunodeficiency Virus ,Simian Acquired Immunodeficiency Syndrome ,Fluorescent Antibody Technique ,MESH: Algorithms ,MESH: Lymph Nodes ,MESH: Flow Cytometry ,NK cells ,Article ,MESH: Chlorocebus aethiops ,Chlorocebus aethiops ,Animals ,Humans ,MESH: Animals ,MESH: Fluorescent Antibody Technique ,MESH: K562 Cells ,Retrovirus ,MESH: Humans ,MESH: Transcriptome ,MESH: Macaca ,MESH: CD4-Positive T-Lymphocytes ,Cell Differentiation ,Flow Cytometry ,MESH: Male ,Killer Cells, Natural ,[SDV] Life Sciences [q-bio] ,MESH: NK Cell Lectin-Like Receptor Subfamily C ,Viral infection ,MESH: Lymphoid Tissue ,Macaca ,Lymph node ,Female ,Simian Immunodeficiency Virus ,Lymph Nodes ,MESH: Simian Acquired Immunodeficiency Syndrome ,K562 Cells ,NK Cell Lectin-Like Receptor Subfamily C ,Transcriptome ,MESH: Female ,Algorithms - 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., NK cells control SIV infection in secondary lymphoid tissues in the natural host that typically doesn’t progress toward disease. Here the authors show that this control is associated with terminal NK cell differentiation and improved MHC-E-dependent activity lacking in pathogenic SIV infection.
- Published
- 2021