Dendritic cells inhibit the progression of Listeria monocytogenes intracellular infection by retaining bacteria in major histocompatibility complex class II-rich phagosomes and by limiting cytosolic growth.
Dendritic cells inhibit the progression of Listeria monocytogenes intracellular infection by retaining bacteria in major histocompatibility complex class II-rich phagosomes and by limiting cytosolic growth.
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树突状细胞通过将细菌保留在富含主要组织相容性复合物 II 类的吞噬体中并限制胞质生长来抑制单核细胞增生李斯特氏菌细胞内感染的进展。
DOI：
10.1128/iai.01027-09
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发表时间：
2010
影响因子：
3.1
通讯作者：
Hiltbold,ElizabethM
中科院分区：
文献类型：
--
作者：
Westcott,MarlenaM;Henry,CurtisJ;Amis,JacquelineE;Hiltbold,ElizabethM
树突状细胞(DC)为单核细胞增多性李斯特氏菌的生长提供了次优的生态位，李斯特氏菌是一种免疫受损和妊娠宿主的兼性细胞内病原体。这在一定程度上是由于大量细菌未能逃脱到细胞质中，这是由李斯特菌溶血素O(LLO)介导的细胞内生命周期中的一个重要步骤。在这里，我们证明了未能进入骨髓来源的DC胞浆的野生型细菌被保留在LAMP2+隔室中。同源的L.产生LLO蛋白的单核细胞产生菌在DC中有严重的逃逸和生长表型。在最初的2 h内，几乎没有突变细菌进入胞浆，而是在主要组织相容性复合体II+(MHC-II+)H2-DM囊泡中发现，LAMP2+是MHC-II抗原载入室(MIIC)的特征。相反，尽管LLO活性降低，该突变体在骨髓来源的巨噬细胞(BMM)中有轻微的表型。在第一个小时内，DC噬菌体被酸化到比BMM噬菌体平均高半个点的pH。与骨髓间充质干细胞不同，单核细胞在DC中的生长在5h后最小，因此DC在感染后期仍能存活和成熟。综上所述，这些数据与一个模型是一致的，在该模型中，与MHC-II分子获取相关的吞噬体成熟事件为1提供了一个次优环境。单核细胞逃逸到DC胞浆，可能是通过限制LLO的活性。这一点，再加上一种控制感染后期细菌生长的未知机制，在关键的成熟反应期间促进了DC的存活。
Dendritic cells (DC) provide a suboptimal niche for the growth ofListeria monocytogenes, a facultative intracellular bacterial pathogen of immunocompromised and pregnant hosts. This is due in part to a failure of large numbers of bacteria to escape to the cytosol, an essential step in the intracellular life cycle that is mediated by listeriolysin O (LLO). Here, we demonstrate that wild-type bacteria that failed to enter the cytosol of bone marrow-derived DC were retained in a LAMP2+compartment. An isogenicL. monocytogenesstrain that produces an LLO protein with reduced pore-forming activity had a severe escape and growth phenotype in DC. Few mutant bacteria entered the cytosol in the first 2 h and were instead found in LAMP2+, major histocompatibility complex class II+(MHC-II+) H2-DM vesicles characteristic of MHC-II antigen loading compartments (MIIC). In contrast, the mutant had a minor phenotype in bone marrow-derived macrophages (BMM) despite the reduced LLO activity. In the first hour, DC phagosomes acidified to a pH that was, on average, half a point higher than that of BMM phagosomes. Unlike BMM,L. monocytogenesgrowth in DC was minimal after 5 h, and consequently, DC remained viable and matured late in infection. Taken together, the data are consistent with a model in which phagosomal maturation events associated with the acquisition of MHC-II molecules present a suboptimal environment forL. monocytogenesescape to the DC cytosol, possibly by limiting the activity of LLO. This, in combination with an undefined mechanism that controls bacterial growth late in infection, promotes DC survival during the critical maturation response.