Enhanced Signaling Through the TLR9 Pathway Is Associated With Resistance to HIV-1 Infection in Chinese HIV-1-Exposed Seronegative Individuals
Enhanced Signaling Through the TLR9 Pathway Is Associated With Resistance to HIV-1 Infection in Chinese HIV-1-Exposed Seronegative Individuals
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通过 TLR9 途径增强的信号传导与中国 HIV-1 暴露血清阴性个体对 HIV-1 感染的抵抗力相关
DOI：
10.3389/fimmu.2020.01050
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发表时间：
2020-05-29
影响因子：
7.3
通讯作者：
Ye, Li
中科院分区：
文献类型：
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作者：
Jiang, Junjun;Hu, Xi;Ye, Li
先天免疫是抵御入侵病原体的第一道防线，可能介导 HIV-1 暴露血清阴性 (HESN) 个体的 HIV-1 抵抗力。本研究旨在确定中国 HESN 个体赋予天然 HIV-1 抵抗力的先天免疫成分。具体来说，我们比较了从 HESN 和对照个体获得的外周血单核细胞 (PBMC)、单核细胞/巨噬细胞和血浆中 Toll 样受体 (TLR) 和相关途径分子的表达水平。 HESN 个体的 PBMC 和血浆中 TLR9、IRF7、IFN-α/β、RANTES 和 MIP-1 α/1β 的表达高于对照受试者。在 TLR9 刺激后，与对照个体的相应细胞相比，在 HESN 个体的 PBMC 和单核细胞/巨噬细胞中观察到 TLR9 和 IRF7 的表达显着更高，并且 IFN-α/β、RANTES 和 MIP-1 α/1β 的产生更高。更重要的是，无论有无TLR9刺激，来自HESN个体的单核细胞源性巨噬细胞(MDM)中的HIV-1复制水平均显着低于来自对照个体的MDM中的HIV-1复制水平。这些数据表明，TLR9 活性的增加和随后抗病毒因子的释放有助于 HESN 个体免受 HIV-1 感染。
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-alpha/beta, RANTES, and MIP-1 alpha/1 beta in PBMCs and plasma than control subjects. Upon TLR9 stimulation, significantly higher expression of TLR9 and IRF7, as well as higher production of IFN-alpha/beta, RANTES, and MIP-1 alpha/1 beta, 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.