Schnettger Laura, Rodgers Angela, Repnik Urska, Lai Rachel P, Pei Gang, Verdoes Martijn, Wilkinson Robert J, Young Douglas B, Gutierrez Maximiliano G
Host-Pathogen Interactions In Tuberculosis Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Mycobacterial Systems Biology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Cell Host Microbe. 2017 May 10;21(5):619-628.e5. doi: 10.1016/j.chom.2017.04.004.
The intracellular pathogen Mycobacterium tuberculosis (Mtb) lives within phagosomes and also disrupts these organelles to access the cytosol. The host pathways and mechanisms that contribute to maintaining Mtb phagosome integrity have not been investigated. Here, we examined the spatiotemporal dynamics of Mtb-containing phagosomes and identified an interferon-gamma-stimulated and Rab20-dependent membrane trafficking pathway in macrophages that maintains Mtb in spacious proteolytic phagolysosomes. This pathway functions to promote endosomal membrane influx in infected macrophages, and is required to preserve Mtb phagosome integrity and control Mtb replication. Rab20 is specifically and significantly upregulated in the sputum of human patients with active tuberculosis. Altogether, we uncover an immune-regulated cellular pathway of defense that promotes maintenance of Mtb within intact membrane-bound compartments for efficient elimination.
细胞内病原体结核分枝杆菌（Mtb）寄生于吞噬体中，还会破坏这些细胞器以进入细胞质。有助于维持Mtb吞噬体完整性的宿主途径和机制尚未得到研究。在此，我们研究了含Mtb吞噬体的时空动态，并在巨噬细胞中鉴定出一种受干扰素-γ刺激且依赖Rab20的膜运输途径，该途径将Mtb维持在宽敞的蛋白水解性吞噬溶酶体中。该途径的作用是促进感染巨噬细胞内体膜的流入，对于维持Mtb吞噬体的完整性和控制Mtb复制是必需的。Rab20在活动性肺结核人类患者的痰液中特异性且显著上调。总之，我们发现了一种免疫调节的细胞防御途径，该途径促进Mtb在完整的膜结合区室中维持，以便有效清除。
