Understanding why the response to infection varies between individuals remains one of the major challenges in immunology and infection biology. A substantial proportion of this heterogeneity can be explained by individual genetic differences which result in variable immune responses, and there are many examples of polymorphisms in nuclear-encoded genes that alter immunocompetence. However, how immunity is affected by genetic polymorphism in an additional genome, inherited maternally inside mitochondria (mtDNA), has been relatively understudied. Mitochondria are increasingly recognized as important mediators of innate immune responses, not only because they are the main source of energy required for costly immune responses, but also because by-products of mitochondrial metabolism, such as reactive oxygen species (ROS), may have direct microbicidal action. Yet, it is currently unclear how naturally occurring variation in mtDNA contributes to heterogeneity in infection outcomes. In this review article, we describe potential sources of variation in mitochondrial function that may arise due to mutations in vital nuclear and mitochondrial components of energy production or due to a disruption in mito-nuclear crosstalk. We then highlight how these changes in mitochondrial function can impact immune responses, focusing on their effects on ATP- and ROS-generating pathways, as well as immune signaling. Finally, we outline how being a powerful and genetically tractable model of infection, immunity and mitochondrial genetics makes the fruit fly Drosophila melanogaster ideally suited to dissect mitochondrial effects on innate immune responses to infection.

了解为什么个体对感染的反应不同仍然是免疫学和感染生物学的主要挑战之一。这种异质性的很大一部分可以用导致不同免疫反应的个体遗传差异来解释，并且有许多改变免疫能力的核编码基因多态性的例子。然而，对于线粒体内母体遗传的额外基因组（mtDNA）的遗传多态性如何影响免疫力的研究相对较少。线粒体越来越被认为是先天免疫反应的重要介质，不仅因为它们是昂贵的免疫反应所需的主要能量来源，而且还因为线粒体代谢的副产物，例如活性氧（ROS），可能具有直接的作用。杀菌作用。然而，目前尚不清楚线粒体 DNA 自然发生的变异如何导致感染结果的异质性。在这篇综述文章中，我们描述了线粒体功能变异的潜在来源，这些变异可能是由于能量产生的重要核和线粒体成分的突变或线粒体核串扰的破坏而引起的。然后，我们强调线粒体功能的这些变化如何影响免疫反应，重点关注它们对 ATP 和 ROS 生成途径以及免疫信号传导的影响。最后，我们概述了果蝇如何成为一种强大且遗传上易于处理的感染、免疫和线粒体遗传学模型黑腹果蝇非常适合剖析线粒体对感染先天免疫反应的影响。