Monlun Marie, Hyernard Caroline, Blanco Patrick, Lartigue Lydia, Faustin Benjamin
Bordeaux University, CIRID, 33000 Bordeaux, France; CNRS, UMR 5164, 146 rue Léo Saignat, 33076 Bordeaux, France.
Bordeaux University, CIRID, 33000 Bordeaux, France; CNRS, UMR 5164, 146 rue Léo Saignat, 33076 Bordeaux, France; Centre Hospitalier Universitaire de Bordeaux, Place Amélie Raba Léon, 33076 Bordeaux, France.
J Mol Biol. 2017 Jan 6;429(1):1-13. doi: 10.1016/j.jmb.2016.10.028. Epub 2016 Oct 27.
The immune system of vertebrates confers protective mechanisms to the host through the sensing of stress-induced agents expressed during infection or cell stress. Among them, the first line of host defense composed of the innate immune sensing of these agents by pattern recognition receptors enables downstream adaptive immunity to be primed, mediating the body's appropriate response to clear infection and tissue damage. Mitochondria are «bacteria within» that allowed the emergence of functional eukaryotic cells by positioning themselves as the cell powerhouse and an initiator of cell death programs. It is striking to consider that such ancestral bacteria, which had to evade host defense at some point to develop evolutionary endosymbiosis, have become instrumental for the modern eukaryotic cell in alerting the immune system against various insults including infection by other pathogens. Mitochondria have indeed become critical regulators of innate immune responses to both pathogens and cell stress. They host numerous modulators, which play a direct role into the assembly of innate sensing machineries that trigger host immune response in both sterile and non-sterile conditions. Several lines of evidence indicate the existence of a complex molecular interplay between mechanisms involved in inflammation and metabolism. Mitochondrial function seems to participate in innate immunity at various stages as diverse as the transcriptional regulation of inflammatory cytokines and chemokines and their maturation by inflammasomes. Here, we review the mechanisms by which mitochondria orchestrate innate immune responses at different levels by promoting a cellular metabolic reprogramming and the cytosolic immune signaling cascades.
脊椎动物的免疫系统通过感知感染或细胞应激期间表达的应激诱导因子，为宿主提供保护机制。其中，由模式识别受体对这些因子进行先天免疫感知所组成的宿主防御第一道防线，能够启动下游适应性免疫，介导身体对清除感染和组织损伤做出适当反应。线粒体是“细胞内的细菌”，它们通过定位为细胞的能量工厂和细胞死亡程序的启动者，使得功能性真核细胞得以出现。令人惊讶的是，这样一种在进化过程中为了发展内共生而必须在某个时候逃避宿主防御的原始细菌，如今却在提醒免疫系统抵御包括其他病原体感染在内的各种损伤方面，对现代真核细胞发挥着重要作用。线粒体确实已成为对病原体和细胞应激的先天免疫反应的关键调节因子。它们含有众多调节因子，这些调节因子在无菌和非无菌条件下触发宿主免疫反应的先天传感机制的组装过程中发挥着直接作用。多条证据表明，炎症和代谢相关机制之间存在复杂的分子相互作用。线粒体功能似乎在炎症细胞因子和趋化因子的转录调控以及它们通过炎性小体成熟等不同阶段参与先天免疫。在此，我们综述线粒体通过促进细胞代谢重编程和胞质免疫信号级联反应在不同水平协调先天免疫反应的机制。
