Abstract
Dendritic cells (DCs), as well as complement, play a major role during human immunodeficiency virus 1 (HIV-1) entry and infection at mucosal sites. Together, DCs and complement are key points for understanding host defence against HIV-1 infection and for studying the impact of new drugs on the regulation of innate host-pathogen interactions and adaptive immunity. For this, we evaluated the antiviral effect of the P80 natural essence (Longan extract) on interactions of non- and complement-opsonized HIV-1 with DCs. In viability assays, we first illustrated the effects of P80 natural essence on DC function. We found that P80 concentrations above 1.5% caused increased cell death, while at concentrations between 0.5% and 1% the compound exerted efficient antiviral effects in DCs and illustrated an adjuvant effect regarding DC activation. DC maturation, as well as co-stimulatory capacity, were significantly improved by P80 natural essence via p38 MAPK phosphorylation in presence of the viral challenge independent of the opsonization pattern. These findings might be exploited for future therapeutic options to target DC subsets directly at mucosal sites by P80 natural essence and to block entry of both, non- and complement-opsonized HIV-1.
Highlights
Published: 31 August 2021 chronic viral diseases, such as human immunodeficiency virus 1 (HIV-1) or HCV, can be treated very efficiently, the use of drugs such as RT or protease inhibitors is associated with significant side effects and very high treatment costs
Incoming pathogens are recognized by antigen-presenting cells such as dermal Dendritic cells (DCs), Langerhans Cells (LCs) or macrophages via an array of pattern-recognition receptors (PRRs), including Toll-like receptors (TLRs), C-type lectin receptors (CLRs) and importantly complement receptors (CRs)
When exposed to HIV-1 surrounded by covalently linked complement C3 fragments DCs were shown to produce innate cytokines including type I interferons (IFN-α, IFN-β), Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
Summary
Chronic viral diseases, such as HIV-1 or HCV, can be treated very efficiently, the use of drugs such as RT or protease inhibitors is associated with significant side effects and very high treatment costs. Interferon-stimulated genes (ISGs), pro-inflammatory cytokines (IL-1β, IL-6, IL-23) and the complement anaphylatoxin C3a [8,9] Such complement-opsonized HIV-1 (HIV-C) in addition mediated significantly enhanced DC infection, DC maturation and stimulation of efficient HIV-1-specific CTL responses [8,11]. The P80 natural essence exerted an adjuvant role during exposure of DCs to both, non- and complement-opsonized HIV-1, and significantly increased DC maturation for non-opsonized HIV-1. It completely abrogated infection of DCs with both, HIV and HIV-C, despite neither mediating virolysis nor lowering viral binding to the most prominent antigen-presenting cells.
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