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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02677

Mass cytometry analysis reveals complex cell-state modifications of blood myeloid cells during HIV infection

Sixtine Coindre1,  Nicolas Tchitchek1, Lamine Alaoui1,  Bruno Vaslin1,  Christine Bourgeois1, Cecile Goujard2,  Camille Lecuroux1, Pierre Bruhns3,  Roger Le Grand1,  Anne-Sophie BEIGNON1,  Olivier Lambotte1, 2 and  Benoit Favier1*
  • 1INSERM U1184 Centre de recherche en Immunologie des Infections virales et des maladies auto-immunes, France
  • 2Service de Médecine Interne et Immunologie Clinique, Hôpital Bicêtre, France
  • 3INSERM U1222 Anticorps en Thérapie et Pathologie, France

Dendritic cells (DC), which are involved in orchestrating early immune responses against pathogens, are dysregulated in their function by HIV infection. This dysregulation likely contributes to tip the balance toward viral persistence. Different DC subpopulations, including classical (cDCs) and plasmacytoid (pDCs) dendritic cells, are subjected to concomitant inflammatory and immunoregulatory events during HIV infection, which hampers the precise characterization of their regulation through classical approaches. Here, we carried out mass cytometry analysis of blood samples from early HIV-infected patients that were longitudinally collected before and after one year of effective combination antiretroviral therapy (cART). Blood samples from HIV controller patients who naturally control the infection were also included. Our data revealed that plasma HIV RNA level was positively associated with a loss of cDC and pDC subpopulations that display high expression of LILR immunomodulatory receptors. Conversely, specific monocyte populations co-expressing high levels of HLA-I, 3 immunomodulatory receptors, CD64, LILRA2 and LILRB4, and the restriction factor CD317, were more abundant in early HIV-infection. Finally, our analysis revealed that the blood of HIV controller patients contained in a higher abundance a particular subtype of CD1c+ cDCs, characterized by elevated co-expression of CD32b inhibitory receptor and HLA-DR antigen-presentation molecules. Overall, this study unravels the modifications induced in DC and monocyte subpopulations in different HIV+ conditions, and provides a better comprehension of the immune regulation/dysregulation mechanisms induced during this viral infection.

Keywords: cyTOF, High dimensional analysis, LILRB1, LILRB2, ILT2, ILT4, CD38, Immune checkpoint, Elite Controllers, Primary HIV infection (PHI), BST2/Tetherin, Fc receptor, LILRA4

Received: 24 Apr 2019; Accepted: 30 Oct 2019.

Copyright: © 2019 Coindre, Tchitchek, Alaoui, Vaslin, Bourgeois, Goujard, Lecuroux, Bruhns, Le Grand, BEIGNON, Lambotte and Favier. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Benoit Favier, INSERM U1184 Centre de recherche en Immunologie des Infections virales et des maladies auto-immunes, Le Kremlin-Bicêtre, France, benoit.favier@cea.fr