Macrophages are a diverse group of phagocytic cells acting in host protection against stress, injury, and pathogens. Here, we show that the scavenger receptor SR-A6 is an entry receptor for human adenoviruses in murine alveolar macrophage-like MPI cells, and important for production of type I interferon. Scavenger receptors contribute to the clearance of endogenous proteins, lipoproteins and pathogens. Knockout of SR-A6 in MPI cells, anti-SR-A6 antibody or the soluble extracellular SR-A6 domain reduced adenovirus type-C5 (HAdV-C5) binding and transduction. Expression of murine SR-A6, and to a lower extent human SR-A6 boosted virion binding to human cells and transduction. Virion clustering by soluble SR-A6 and proximity localization with SR-A6 on MPI cells suggested direct adenovirus interaction with SR-A6. Deletion of the negatively charged hypervariable region 1 (HVR1) of hexon reduced HAdV-C5 binding and transduction, implying that the viral ligand for SR-A6 is hexon. SR-A6 facilitated macrophage entry of HAdV-B35 and HAdV-D26, two important vectors for transduction of hematopoietic cells and human vaccination. The study highlights the importance of scavenger receptors in innate immunity against human viruses.

巨噬细胞是一组多样化的吞噬细胞，可起到保护宿主免受压力、损伤和病原体的作用。在这里，我们表明清道夫受体 SR-A6 是鼠肺泡巨噬细胞样 MPI 细胞中人腺病毒的进入受体，对 I 型干扰素的产生很重要。清道夫受体有助于清除内源性蛋白质、脂蛋白和病原体。在 MPI 细胞中敲除 SR-A6、抗 SR-A6 抗体或可溶性细胞外 SR-A6 结构域会降低腺病毒 C5 型 (HAdV-C5) 的结合和转导。鼠 SR-A6 的表达，以及在较低程度上人类 SR-A6 的表达促进了病毒粒子与人类细胞的结合和转导。可溶性 SR-A6 的病毒粒子聚类和与 SR-A6 在 MPI 细胞上的邻近定位表明腺病毒与 SR-A6 直接相互作用。六邻体带负电荷的高变区 1 (HVR1) 的缺失降低了 HAdV-C5 的结合和转导，这意味着 SR-A6 的病毒配体是六邻体。SR-A6 促进了 HAdV-B35 和 HAdV-D26 的巨噬细胞进入，这是造血细胞转导和人类疫苗接种的两个重要载体。该研究强调了清道夫受体在针对人类病毒的先天免疫中的重要性。