The local environment orchestrates mucosal decidual macrophage differentiation and substantially inhibits HIV-1 replication

Autor: Héloïse Quillay, H. El Costa, Marion Duriez, J Ighil, Romain Marlin, Françoise Barré-Sinoussi, Fahd Benjelloun, C. de Truchis, Elisabeth Menu, Claude Cannou, M. Rahmati, Marie-Thérèse Nugeyre
Přispěvatelé: Régulation des Infections Rétrovirales, Institut Pasteur [Paris], 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), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Antoine Béclère, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by ANRS (HEC and HQfinancial support and grant #12165/13129), Sidaction (HEC and MD financial support and grant# AI20-3-01671), the TOTAL Foundation, INSERM, and Institut Pasteur, Institut Pasteur [Paris] (IP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), MENU, Elisabeth
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Cyclin-Dependent Kinase Inhibitor p21
0301 basic medicine
Cellular differentiation
Immunology
HIV Infections
Biology
Virus Replication
[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity
Interferon-gamma
03 medical and health sciences
0302 clinical medicine
Interferon
Decidua
medicine
Humans
Immunology and Allergy
Macrophage
Interferon gamma
Receptor
Immunity
Mucosal
[SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity
Cells
Cultured
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Macrophages
Cell Differentiation
3. Good health
030104 developmental biology
medicine.anatomical_structure
Cellular Microenvironment
Toll-Like Receptor 7
Viral replication
Toll-Like Receptor 8
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
HIV-1
Female
Ex vivo
030215 immunology
medicine.drug
Zdroj: Mucosal Immunology
Mucosal Immunology, Nature Pub. Group, 2016, 9 (3), pp.634-46. ⟨10.1038/mi.2015.87⟩
Mucosal Immunology, 2016, 9 (3), pp.634-46. ⟨10.1038/mi.2015.87⟩
ISSN: 1933-0219
1935-3456
DOI: 10.1038/mi.2015.87⟩
Popis: International audience; Macrophages from the decidua basalis (dM), the main uterine mucosa during pregnancy, are weakly permissive to HIV-1 infection. Here, we investigated the mechanisms underlying this natural control. We show, by using freshly purified decidual macrophages and ex vivo human decidual explants, that the local decidual environment influences dM differentiation and naturally protects these cells from HIV-1 infection. Interferon (IFN)-γ, present in the decidual tissue, contributes to maintenance of the dM phenotype and restricts HIV-1 infection by mechanisms involving the cyclin-dependent kinase inhibitor p21Cip1/Waf1. We also found that activation of Toll-like receptors 7 and 8 expressed by dM reinforces the low permissivity of dM to HIV-1 by restricting viral replication and inducing secretion of cytokines in the decidual environment, including IFN-γ, that shape dM plasticity. A major challenge for HIV-1 eradication is to control infection of tissue-resident macrophages in the female reproductive tract. Our findings provide clues to the development of novel strategies to prevent HIV-1 macrophage infection.
Databáze: OpenAIRE
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