Moore Elizabeth R, Ouellette Scot P
Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota Vermillion, SD, USA.
Front Cell Infect Microbiol. 2014 Oct 31;4:157. doi: 10.3389/fcimb.2014.00157. eCollection 2014.
Chlamydia is an obligate intracellular pathogen that develops in the host cell in a vacuole termed the chlamydial inclusion. The prevailing concept of the chlamydial inclusion is of a parasitophorous vacuole. Here, the inclusion is the recipient of one-way host-pathogen interactions thus draining nutrients from the cell and negatively impacting it. While Chlamydia orchestrates some aspects of cell function, recent data indicate host cells remain healthy up until, and even after, chlamydial egress. Thus, while Chlamydia relies on the host cell for necessary metabolites, the overall function of the host cell, during chlamydial growth and development, is not grossly disturbed. This is consistent with the obligate intracellular organism's interest to maintain viability of its host. To this end, Chlamydia expresses inclusion membrane proteins, Incs, which serve as molecular markers for the inclusion membrane. Incs also contribute to the physical structure of the inclusion membrane and facilitate host-pathogen interactions across it. Given the function of Incs and the dynamic interactions that occur at the inclusion membrane, we propose that the inclusion behaves similarly to an organelle-albeit one that benefits the pathogen. We present the hypothesis that the chlamydial inclusion acts as a pathogen-specified parasitic organelle. This representation integrates the inclusion within existing subcellular trafficking pathways to divert a subset of host-derived metabolites thus maintaining host cell homeostasis. We review the known interactions of the chlamydial inclusion with the host cell and discuss the role of Inc proteins in the context of this model and how this perspective can impact the study of these proteins. Lessons learnt from the chlamydial pathogen-specified parasitic organelle can be applied to other intracellular pathogens. This will increase our understanding of how intracellular pathogens engage the host cell to establish their unique developmental niches.
衣原体是一种专性细胞内病原体，在宿主细胞内的一个称为衣原体包涵体的液泡中发育。关于衣原体包涵体的主流概念是它是一个寄生泡。在这里，包涵体是单向宿主-病原体相互作用的接受者，从而从细胞中耗尽营养并对其产生负面影响。虽然衣原体协调细胞功能的某些方面，但最近的数据表明，直到衣原体释放甚至释放后，宿主细胞仍保持健康。因此，虽然衣原体依赖宿主细胞获取必需的代谢物，但在衣原体生长和发育过程中，宿主细胞的整体功能并未受到严重干扰。这与这种专性细胞内生物维持其宿主生存能力的利益是一致的。为此，衣原体表达包涵体膜蛋白（Incs），它们作为包涵体膜的分子标记。Incs也有助于包涵体膜的物理结构，并促进跨膜的宿主-病原体相互作用。鉴于Incs的功能以及在包涵体膜上发生的动态相互作用，我们提出包涵体的行为类似于一种细胞器——尽管是一种对病原体有益的细胞器。我们提出假说，衣原体包涵体作为一种病原体指定的寄生细胞器。这种表述将包涵体整合到现有的亚细胞运输途径中，以转移一部分宿主来源的代谢物，从而维持宿主细胞的稳态。我们回顾了衣原体包涵体与宿主细胞的已知相互作用，并在这个模型的背景下讨论了Inc蛋白的作用，以及这种观点如何影响对这些蛋白的研究。从衣原体病原体指定的寄生细胞器中学到的经验教训可以应用于其他细胞内病原体。这将增进我们对细胞内病原体如何与宿主细胞相互作用以建立其独特发育生态位的理解。
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