Co- but not Sequential Infection of DCs Boosts Their HIV-Specific CTL-Stimulatory Capacity
| Autor: | Schönfeld, Manuela, Knackmuss, Ulla, Chandorkar, Parul, Hörtnagl, Paul, Hope, Thomas John, Moris, Arnaud, Bellmann-Weiler, Rosa, Lass-Flörl, Cornelia, Posch, Wilfried, Wilflingseder, Doris |
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| Přispěvatelé: | Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Feinberg School of Medicine, Northwestern University [Evanston], Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11), Université Paris-Saclay, Innsbruck Medical University [Austria] (IMU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Gestionnaire, Hal Sorbonne Université |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
[SDV.IMM] Life Sciences [q-bio]/Immunology
dendritic cell [SDV]Life Sciences [q-bio] Immunology virus diseases HIV Infections T-Cell Antigen Receptor Specificity chemical and pharmacologic phenomena hemic and immune systems Dendritic Cells HLA-DR Antigens Virus Internalization Lymphocyte Activation Virus Replication STIs [SDV] Life Sciences [q-bio] CTL HIV-1 Humans [SDV.IMM]Life Sciences [q-bio]/Immunology Immunology and Allergy complement Biomarkers Original Research T-Lymphocytes Cytotoxic |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, 2019, 10, ⟨10.3389/fimmu.2019.01123⟩ Frontiers in Immunology, Frontiers, 2019, 10, ⟨10.3389/fimmu.2019.01123⟩ |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2019.01123 |
| Popis: | International audience; Pathogenic bacteria and their microbial products activate dendritic cells (DCs) at mucosal surfaces during sexually transmitted infections (STIs) and therefore might also differently shape DC functions during co-infection with HIV-1. We recently illustrated that complement (C) coating of HIV-1 (HIV-C), as primarily found during the acute phase of infection before appearance of HIV-specific antibodies, by-passed SAMHD1-mediated restriction in DCs and therefore mediated an increased DC activation and antiviral capacity. To determine whether the superior antiviral effects of HIV-C-exposed DCs also apply during STIs, we developed a co-infection model in which DCs were infected with Chlamydia spp. simultaneously (HIV-C/Chlam-DCs or HIV/Chlam-DCs) or a sequential infection model, where DCs were exposed to Chlamydia for 3 or 24 h (Chlam-DCs) followed by HIV-1 infection. Co-infection of DCs with HIV-1 and Chlamydia significantly boosted the CTL-stimulatory capacity compared to HIV-1-loaded iDCs and this boost was independent on the opsonization pattern. This effect was lost in the sequential infection model, when opsonized HIV-1 was added delayed to Chlamydia-loaded DCs. The reduction in the CTL-stimulatory capacity of Chlam-DCs was not due to lower HIV-1 binding or infection compared to iDCs or HIV-C/Chlam-DCs, but due to altered fusion and internalization mechanisms within DCs. The CTL-stimulatory capacity of HIV-C in Chlam-DCs correlated with significantly reduced viral fusion compared to iDCs and HIV-C/Chlam-DCs and illustrated considerably increased numbers of HIV-C-containing vacuoles than iDCs. The data indicate that Chlamydia co-infection of DCs mediates a transient boost of their HIV-specific CTL-stimulatory and antiviral capacity, while in the sequential infection model this is reversed and associated with hazard to the host. |
| Databáze: | OpenAIRE |
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