Listeria monocytogenes evades killing by autophagy during colonization of host cells
Listeria monocytogenes evades killing by autophagy during colonization of host cells
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DOI：
10.4161/auto.4450
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发表时间：
2007-09-01
期刊：
影响因子：
13.3
通讯作者：
Brumell, John H.
中科院分区：
文献类型：
--
作者：
Birmingham, Cheryl L.;Canadieni, Veronica;Brumell, John H.
单核细胞增生李斯特氏菌是一种细胞内病原体，能够定植于巨噬细胞的胞质溶胶中。在这里，我们研究了这种病原体与自噬的相互作用，自噬是一种宿主细胞质降解途径，构成针对微生物入侵者先天免疫的重要组成部分。单增李斯特菌感染诱导巨噬细胞自噬系统的激活。感染后 1 小时 (p.i.)，细胞内细菌群（约 37%）与自噬标记物 LC3 共定位。这些细菌位于液泡内，并以 LLO 依赖性方式成为自噬的目标。在感染后期（注射后 4 小时），大多数单核细胞增生李斯特菌逃逸到胞质中并快速复制。此时，只有不到 10% 的细胞内细菌与 LC3 共存。我们发现 ActA 表达足以阻止巨噬细胞胞浆中细菌的自噬。令人惊讶的是，ActA 表达并不是严格必要的，这表明还涉及其他毒力因子。因此，我们还发现细菌磷脂酶 Pl-PLC 和 PC-PLC 在自噬逃避中发挥作用，因为缺乏磷脂酶表达的细菌在感染后期会成为自噬的目标。总之，我们的结果表明，单核细胞增生利斯特氏菌利用多种机制来避免巨噬细胞定植期间自噬系统的破坏。
Listeria monocytogenes is an intracellular pathogen that is able to colonize the cytosol of macrophages. Here we examined the interaction of this pathogen with autophogy, a host cytosolic degradative pathway that constitutes an important component of innate immunity towards microbial invaders. L. monocytogenes infection induced activation of the autophagy system in macrophages. At 1 h post infection (p.i.), a population of intracellular bacteria (similar to 37%) colocalized with the autophagy marker LC3. These bacteria were within vacuoles and were targeted by autophogy in an LLO-dependent manner. At later stages in infection (by 4 h p.i.), the majority of L. monocytogenes escaped into the cytosol and rapidly replicated. At these times, less than 10% of intracellular bacteria colocalized with LC3. We found that ActA expression was sufficient to prevent autophagy of bacteria in the cytosol of macrophages. Surprisingly, ActA expression was not strictly necessary, indicating that other virulence factors were involved. Accordingly, we also found a role for the bacterial phospholipases, Pl-PLC and PC-PLC, in autophogy evasion, as bacteria lacking phospholipase expression were targeted by autophagy at later times in infection. Together, our results demonstrate that L. monocytogenes utilizes multiple mechanisms to avoid destruction by the autophagy system during colonization of macrophages.