Macrophages provide a first line of defense against microorganisms, and while some mechanisms to kill pathogens such as the oxidative burst are well described, others are still undefined or unknown. Here, we report that the Rab32 guanosine triphosphatase and its guanine nucleotide exchange factor BLOC-3 (biogenesis of lysosome-related organelles complex–3) are central components of a trafficking pathway that controls both bacterial and fungal intracellular pathogens. This host-defense mechanism is active in both human and murine macrophages and is independent of well-known antimicrobial mechanisms such as the NADPH (reduced form of nicotinamide adenine dinucleotide phosphate)–dependent oxidative burst, production of nitric oxide, and antimicrobial peptides. To survive in human macrophages, Salmonella Typhi actively counteracts the Rab32/BLOC-3 pathway through its Salmonella pathogenicity island-1–encoded type III secretion system. These findings demonstrate that the Rab32/BLOC-3 pathway is a novel and universal host-defense pathway and protects mammalian species from various pathogens.

巨噬细胞提供了抵御微生物的第一道防线，虽然一些杀死病原体的机制（如氧化爆发）已得到很好的描述，但其他一些机制仍未确定或未知。在这里，我们报告说 Rab32 鸟苷三磷酸酶及其鸟嘌呤核苷酸交换因子 BLOC-3（溶酶体相关细胞器复合物的生物合成-3）是控制细菌和真菌细胞内病原体的运输途径的核心成分。这种宿主防御机制在人和鼠巨噬细胞中都很活跃，并且独立于众所周知的抗菌机制，例如 NADPH（烟酰胺腺嘌呤二核苷酸磷酸盐的还原形式）依赖的氧化爆发、一氧化氮的产生和抗菌肽。为了在人类巨噬细胞中生存，沙门氏菌伤寒通过其沙门氏菌致病性 island-1 编码的 III 型分泌系统积极抵消 Rab32/BLOC-3 途径。这些发现表明，Rab32/BLOC-3 途径是一种新型的通用宿主防御途径，可保护哺乳动物物种免受各种病原体的侵害。