Brucella evades macrophage killing via VirB-dependent sustained interactions with the endoplasmic reticulum.
Brucella evades macrophage killing via VirB-dependent sustained interactions with the endoplasmic reticulum.
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DOI：
10.1084/jem.20030088
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发表时间：
2003-08-18
期刊：
影响因子：
--
通讯作者：
Gorvel JP
中科院分区：
文献类型：
--
作者：
Celli J;de Chastellier C;Franchini DM;Pizarro-Cerda J;Moreno E;Gorvel JP
细胞内病原体布鲁氏菌是布鲁氏菌病的病原体，布鲁氏菌病是一种影响包括人类在内的哺乳动物的世界性人畜共患病。布鲁氏菌毒力的关键是其在宿主巨噬细胞内存活和复制的能力，但复制区室的潜在机制和性质仍不清楚。在这里，我们表明，在小鼠骨髓源性巨噬细胞的布鲁氏菌感染模型中，一部分在初始巨噬细胞杀伤中存活的细菌继续在与内吞途径隔离的隔室中复制。布鲁氏菌空泡的成熟涉及与内质网（ER）的持续相互作用和融合，这产生了具有ER样特性的复制区室。通过复制布鲁氏菌获得ER膜不依赖于ER-高尔基体COPI依赖的囊泡转运。细胞内生存所必需的VirB IV型分泌系统的突变体不能维持与ER的相互作用和融合，并通过最终与溶酶体融合而被杀死。因此，我们证明，活细胞内布鲁氏菌逃避巨噬细胞通过VirB依赖的持续相互作用与ER。此外，我们分配的VirB系统的细胞内功能，作为所需的后期成熟事件所必需的ER衍生的复制细胞器的生物合成。
The intracellular pathogen Brucella is the causative agent of brucellosis, a worldwide zoonosis that affects mammals, including humans. Essential to Brucella virulence is its ability to survive and replicate inside host macrophages, yet the underlying mechanisms and the nature of the replicative compartment remain unclear. Here we show in a model of Brucella abortus infection of murine bone marrow–derived macrophages that a fraction of the bacteria that survive an initial macrophage killing proceed to replicate in a compartment segregated from the endocytic pathway. The maturation of the Brucella-containing vacuole involves sustained interactions and fusion with the endoplasmic reticulum (ER), which creates a replicative compartment with ER-like properties. The acquisition of ER membranes by replicating Brucella is independent of ER-Golgi COPI-dependent vesicular transport. A mutant of the VirB type IV secretion system, which is necessary for intracellular survival, was unable to sustain interactions and fuse with the ER, and was killed via eventual fusion with lysosomes. Thus, we demonstrate that live intracellular Brucella evade macrophage killing through VirB-dependent sustained interactions with the ER. Moreover, we assign an intracellular function to the VirB system, as being required for late maturation events necessary for the biogenesis of an ER-derived replicative organelle.
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影响因子：
7.8
作者：
Abrami, L;Fivaz, M;Glauser, PE;Parton, RG;van der Goot, FG
通讯作者：
van der Goot, FG
影响因子：
3.6
作者：
O'Callaghan, D;Cazevieille, C;Ramuz, M
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Ramuz, M
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3.4
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Ugalde, RA
影响因子：
3.1
作者：
Naroeni, A;Jouy, N;Porte, F
通讯作者：
Porte, F
影响因子：
3.1
作者：
Arenas, GN;Staskevich, AS;Mayorga, LS
通讯作者：
Mayorga, LS