Eisenreich Wolfgang, Rudel Thomas, Heesemann Jürgen, Goebel Werner
Department of Chemistry, Chair of Biochemistry, Technische Universität MünchenGarching, Germany.
Department of Microbiology, Biocenter, University of WürzburgWürzburg, Germany.
Front Cell Infect Microbiol. 2017 Jul 13;7:316. doi: 10.3389/fcimb.2017.00316. eCollection 2017.
Intracellular bacterial pathogens (IBPs) invade and replicate in different cell types including immune cells, in particular of the innate immune system (IIS) during infection in the acute phase. However, immune cells primarily function as essential players in the highly effective and integrated host defense systems comprising the IIS and the adaptive immune system (AIS), which cooperatively protect the host against invading microbes including IBPs. As countermeasures, the bacterial pathogens (and in particular the IBPs) have developed strategies to evade or reprogram the IIS at various steps. The intracellular replication capacity and the anti-immune defense responses of the IBP's as well as the specific antimicrobial responses of the immune cells of the innate and the AIS depend on specific metabolic programs of the IBPs and their host cells. The metabolic programs of the immune cells supporting or counteracting replication of the IBPs appear to be mutually exclusive. Indeed, recent studies show that upon interaction of naïve, metabolically quiescent immune cells with IBPs, different metabolic activation processes occur which may result in the provision of a survival and replication niche for the pathogen or its eradication. It is therefore likely that within a possible host cell population subsets exist that are metabolically programmed for pro- or anti-microbial conditions. These metabolic programs may be triggered by the interactions between different bacterial agonistic components and host cell receptors. In this review, we summarize the current status in the field and discuss metabolic adaptation processes within immune cells of the IIS and the IBPs that support or restrict the intracellular replication of the pathogens.
细胞内细菌病原体（IBP）在急性期感染期间侵入并在包括免疫细胞在内的不同细胞类型中复制，尤其是在天然免疫系统（IIS）的免疫细胞中。然而，免疫细胞主要作为高效且整合的宿主防御系统中的关键参与者，该系统由IIS和适应性免疫系统（AIS）组成，它们协同保护宿主抵御包括IBP在内的入侵微生物。作为应对措施，细菌病原体（特别是IBP）已制定策略，在各个步骤中规避或重新编程IIS。IBP的细胞内复制能力、抗免疫防御反应以及天然免疫细胞和AIS免疫细胞的特异性抗菌反应取决于IBP及其宿主细胞的特定代谢程序。支持或对抗IBP复制的免疫细胞代谢程序似乎是相互排斥的。事实上，最近的研究表明，未激活的、代谢静止的免疫细胞与IBP相互作用时，会发生不同的代谢激活过程，这可能为病原体提供生存和复制的生态位，或者导致其被根除。因此，在可能的宿主细胞群体中，很可能存在针对促微生物或抗微生物条件进行代谢编程的亚群。这些代谢程序可能由不同细菌激动成分与宿主细胞受体之间的相互作用触发。在本综述中，我们总结了该领域的现状，并讨论了IIS免疫细胞和IBP中支持或限制病原体细胞内复制的代谢适应过程。
