While tuberculosis (TB) is a risk factor in HIV-1-infected individuals, the mechanisms by which Mycobacterium tuberculosis (Mtb) worsens HIV-1 pathogenesis remain scarce. We showed that HIV-1 infection is exacerbated in macrophages exposed to TB-associated microenvironments due to tunneling nanotube (TNT) formation. To identify molecular factors associated with TNT function, we performed a transcriptomic analysis in these macrophages, and revealed the up-regulation of Siglec-1 receptor. Siglec-1 expression depends on Mtb-induced production of type I interferon (IFN-I). In co-infected non-human primates, Siglec-1 is highly expressed by alveolar macrophages, whose abundance correlates with pathology and activation of IFN-I/STAT1 pathway. Siglec-1 localizes mainly on microtubule-containing TNT that are long and carry HIV-1 cargo. Siglec-1 depletion decreases TNT length, diminishes HIV-1 capture and cell-to-cell transfer, and abrogates the exacerbation of HIV-1 infection induced by Mtb. Altogether, we uncover a deleterious role for Siglec-1 in TB-HIV-1 co-infection and opens new avenues to understand TNT biology.

中文翻译：

---

结核相关的IFN-I在隧道纳米管上诱导Siglec-1，并促进HIV-1在巨噬细胞中的传播。

结核病（TB）是感染HIV-1的个体的危险因素，但结核分枝杆菌的发病机制（MTB）恶化HIV-1的发病机制仍然稀缺。我们显示，由于隧穿纳米管（TNT）的形成，暴露于TB相关微环境的巨噬细胞中HIV-1感染加剧。为了确定与TNT功能相关的分子因素，我们在这些巨噬细胞中进行了转录组分析，并揭示了Siglec-1受体的上调。Siglec-1表达取决于Mtb诱导的I型干扰素（IFN-I）产生。在共同感染的非人类灵长类动物中，Siglec-1被肺泡巨噬细胞高度表达，其丰度与病理和IFN-I / STAT1途径的激活有关。Siglec-1主要定位在长且携带HIV-1货物的含微管的TNT上。Siglec-1耗竭减少了TNT长度，减少了HIV-1捕获和细胞间转移，并消除了由Mtb引起的HIV-1感染的恶化。总之，我们发现了Siglec-1在TB-HIV-1共感染中的有害作用，并开辟了了解TNT生物学的新途径。