| Autor: |
Nijmeijer BM; Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands., Bermejo-Jambrina M; Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands.; Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria., Kaptein TM; Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands., Ribeiro CMS; Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands., Wilflingseder D; Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria. doris.wilflingseder@i-med.ac.at., Geijtenbeek TBH; Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands. t.b.geijtenbeek@amsterdamumc.nl. |
| Abstrakt: |
Semen is important in determining HIV-1 susceptibility but it is unclear how it affects virus transmission during sexual contact. Mucosal Langerhans cells (LCs) are the first immune cells to encounter HIV-1 during sexual contact and have a barrier function as LCs are restrictive to HIV-1. As semen from people living with HIV-1 contains complement-opsonized HIV-1, we investigated the effect of complement on HIV-1 dissemination by human LCs in vitro and ex vivo. Notably, pre-treatment of HIV-1 with semen enhanced LC infection compared to untreated HIV-1 in the ex vivo explant model. Infection of LCs and transmission to target cells by opsonized HIV-1 was efficiently inhibited by blocking complement receptors CR3 and CR4. Complement opsonization of HIV-1 enhanced uptake, fusion, and integration by LCs leading to an increased transmission of HIV-1 to target cells. However, in the absence of both CR3 and CR4, C-type lectin receptor langerin was able to restrict infection of complement-opsonized HIV-1. These data suggest that complement enhances HIV-1 infection of LCs by binding CR3 and CR4, thereby bypassing langerin and changing the restrictive nature of LCs into virus-disseminating cells. Targeting complement factors might be effective in preventing HIV-1 transmission. |
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