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Τετάρτη 21 Μαρτίου 2018

Expression of complement receptor 3 (CR3) and regulatory protein CD46 on dendritic cells of antiretroviral naïve and treated HIV-1 infected individuals: Correlation with immune activation status

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Publication date: April 2018
Source:Molecular Immunology, Volume 96
Author(s): Nitesh Mishra, Madhav Mohata, Heena Aggarwal, Omkar Chaudhary, Bimal Kumar Das, Sanjeev Sinha, Anjali Hazarika, Kalpana Luthra
During infection and budding, human immunodeficiency virus-1 (HIV-1) acquires regulators of Complement Activation (RCAs) along with the host cell membrane on the viral envelope. Activation of host complement system results in opsonization of virus by complement fragments, however the virus evades complement mediated lysis (CoML) by virtue of the RCAs on the viral envelope. The RCAs on HIV-1 envelope process complement protein C3 into various fragments that promote viral entry and infection of cells through different complement receptors. Complement opsonized HIV-1 has been shown in vitro to infect dendritic cells (DCs) in a CR3 dependent manner, although the role of CR3 and CD46 in natural HIV-1 infection is not clear. Surface expression of CR3 and CD46 on DC subsets of 30 antiretroviral naïve, 31 treated (cART) HIV-1 infected individuals and 30 seronegative controls was measured by flow cytometry and plasma levels of cytokines and complement activity (C3c levels) were quantitated by sandwich ELISA. Significantly lower surface expression of CR3 and CD46 was observed on DC subsets in naïve and treated HIV-1 infected individuals compared to controls. Significantly higher complement activation and plasma levels of IL-4, IL-8, IL-10 and IFN-γ were observed in treatment naïve HIV-1 infected individuals than controls. Significantly lower plasma levels of IL-4, IL-6, IL-8 and IL-10 were observed in treated vs. naïve HIV-1 infected individuals. Our findings suggest that alterations in expression of CR3 and CD46 on DCs along with complement activity could be factors that influence viral persistence and HIV-1 disease progression and need to be further evaluated.



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