Abstract
Innate immunity is the first line of defense against invading pathogens and may mediate HIV-1 resistance in HIV-1–exposed seronegative (HESN) individuals. This study aims to identify components of innate immunity that confer natural HIV-1 resistance in Chinese HESN individuals. Specifically, we compared the expression levels of Toll-like receptors (TLRs) and associated pathway molecules in peripheral blood mononuclear cells (PBMCs), monocytes/macrophages, and plasma obtained from HESN and control individuals. HESN individuals had higher expression of TLR9, IRF7, IFN-α/β, RANTES, and MIP-1α/1β in PBMCs and plasma than control subjects. Upon TLR9 stimulation, significantly higher expression of TLR9 and IRF7, as well as higher production of IFN-α/β, RANTES, and MIP-1α/1β, was observed in PBMCs and monocytes/macrophages from HESN individuals than in the corresponding cells from control individuals. More importantly, both with and without TLR9 stimulation, the levels of HIV-1 replication in monocyte-derived macrophages (MDMs) from HESN individuals were significantly lower than those in MDMs from control individuals. These data suggest that increased TLR9 activity and subsequent release of antiviral factors contribute to protection against HIV-1 in HESN individuals.
Highlights
Since the emergence of the global HIV/AIDS epidemic, HIV/AIDS has caused more than 20 million deaths [1]
Because IFN-α/β expression is induced by activation of Toll-like receptors (TLRs) pathways and by many other HIV-1–recognizing Pattern recognition receptors (PRRs), including SAMHD1, interferon-inducible protein 16 (IFI16), cyclic GMP-AMP synthase (cGAS), STING, RIG-I, MDA-5, TLR3, TLR7, TLR8, we investigated these expression levels in HIV-1–exposed seronegative (HESN) and control subjects
Several studies have examined the relationships between host innate immunity and HIV resistance in HESN individuals
Summary
Since the emergence of the global HIV/AIDS epidemic, HIV/AIDS has caused more than 20 million deaths [1]. There are no effective medicines to cure HIV/AIDS or vaccines to provide comprehensive protection against infection. Understanding the mechanism of resistance to HIV acquisition in HESN individuals is critical for providing new insight into HIV transmission and would facilitate the development of novel drugs, vaccines, or microbicidal approaches. To date, only homozygosity for the CCR5 32 mutation [11] has been consistently identified as a mechanism of HIV resistance. This mutation accounts for only a minority of cases; in particular, it has rarely been found in the Chinese population. The precise mechanisms of protection against HIV in most HESN individuals remain to be determined
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