A variety of signals influence the capacity of dendritic cells (DCs) to mount potent antiviral cytotoxic T-cell (CTL) responses. In particular, innate immune sensing by pathogen recognition receptors, such as TLR and C-type lectines, influences DC biology and affects their susceptibility to HIV infection. Yet, whether the combined effects of PPRs triggering and HIV infection influence HIV-specific (HS) CTL responses remain enigmatic. Here, we dissect the impact of innate immune sensing by pathogen recognition receptors on DC maturation, HIV infection, and on the quality of HS CTL activation. Remarkably, ligand-driven triggering of TLR-3, -4, NOD2, and DC-SIGN, despite reducing viral replication, markedly increased the capacity of infected DCs to stimulate HS CTLs. This was exemplified by the diversity and the quantity of cytokines produced by HS CTLs primed by these DCs. Infecting DCs with viruses harboring members of the APOBEC family of antiviral factors enhanced the antigen-presenting skills of infected DCs. Our results highlight the tight interplay between innate and adaptive immunity and may help develop innovative immunotherapies against viral infections.

中文翻译：

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触发 TLR-3、-4、NOD2 和 DC-SIGN 可减少病毒复制并增加 HIV 感染的人类树突状细胞的 T 细胞激活能力。


多种信号影响树突状细胞 (DC) 发起有效抗病毒细胞毒性 T 细胞 (CTL) 反应的能力。特别是，病原体识别受体（例如 TLR 和 C 型凝集素）的先天免疫感应会影响 DC 生物学并影响其对 HIV 感染的易感性。然而，PPR 触发和 HIV 感染的联合效应是否会影响 HIV 特异性 (HS) CTL 反应仍然是个谜。在这里，我们剖析了病原体识别受体的先天免疫感应对 DC 成熟、HIV 感染和 HS CTL 激活质量的影响。值得注意的是，配体驱动的 TLR-3、-4、NOD2 和 DC-SIGN 触发，尽管减少了病毒复制，但显着增加了受感染 DC 刺激 HS CTL 的能力。由这些 DC 引发的 HS CTL 产生的细胞因子的多样性和数量证明了这一点。用含有 APOBEC 抗病毒因子家族成员的病毒感染 DC，增强了受感染 DC 的抗原呈递能力。我们的结果强调了先天免疫和适应性免疫之间的紧密相互作用，可能有助于开发针对病毒感染的创新免疫疗法。