Uncharted territory: the role of mitochondrial DNA variation in macrophage-mediated host susceptibility to tuberculosis

IF 2.9 3区医学 Q3 IMMUNOLOGY

Tuberculosis Pub Date : 2025-05-08 DOI:10.1016/j.tube.2025.102650

Dayna Croock , Yolandi Swart , Tomasz Janusz Sanko , Vuyo Mavumengwana , Marlo Möller , Caitlin Uren , Desiree C. Petersen

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引用次数: 0

Abstract

Mitochondria form an integral, yet frequently underappreciated, part of the immune response to Mycobacterium tuberculosis (M.tb), particularly within macrophages. Despite growing recognition for their role in infection and immunity, studies investigating how mitochondrial DNA (mtDNA) variation influences host susceptibility to tuberculosis (TB) are limited. Notably, there are no studies in African-based populations, although Africans possess unparalleled human genetic diversity, including the earliest diverged mitochondrial haplogroups, and a high TB burden. This underrepresentation limits the discovery of novel ancestry-specific genetic loci associated with TB. In this review article, we describe the unique characteristics of mtDNA, highlight key mitochondrial functions relevant to macrophage responses during M.tb infection, and summarise published studies that investigate the role of host mtDNA variation in TB susceptibility. We further advocate for the inclusion of African populations in future studies to identify novel TB susceptibility genetic risk loci and expand the current knowledgebase on host TB susceptibility.

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未知领域：线粒体DNA变异在巨噬细胞介导的宿主对结核病易感性中的作用

线粒体在对结核分枝杆菌（M.tb）的免疫反应中，尤其是在巨噬细胞中，是一个不可缺少的，但经常被低估的组成部分。尽管人们越来越认识到线粒体DNA （mtDNA）变异在感染和免疫中的作用，但关于线粒体DNA （mtDNA）变异如何影响宿主对结核病（TB）易感性的研究有限。值得注意的是，没有针对非洲人口的研究，尽管非洲人拥有无与伦比的人类遗传多样性，包括最早分化的线粒体单倍群，以及较高的结核病负担。这种代表性不足限制了发现与结核病相关的新的祖先特异性遗传位点。在这篇综述文章中，我们描述了mtDNA的独特特征，强调了与结核分枝杆菌感染期间巨噬细胞反应相关的关键线粒体功能，并总结了研究宿主mtDNA变异在结核易感性中的作用的已发表研究。我们进一步提倡在未来的研究中纳入非洲人群，以确定新的结核病易感性遗传风险位点，并扩大目前关于宿主结核病易感性的知识库。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Tuberculosis 医学-呼吸系统

CiteScore

4.60

自引率

3.10%

发文量

审稿时长

49 days

期刊介绍： Tuberculosis is a speciality journal focusing on basic experimental research on tuberculosis, notably on bacteriological, immunological and pathogenesis aspects of the disease. The journal publishes original research and reviews on the host response and immunology of tuberculosis and the molecular biology, genetics and physiology of the organism, however discourages submissions with a meta-analytical focus (for example, articles based on searches of published articles in public electronic databases, especially where there is lack of evidence of the personal involvement of authors in the generation of such material). We do not publish Clinical Case-Studies. Areas on which submissions are welcomed include: -Clinical TrialsDiagnostics- Antimicrobial resistance- Immunology- Leprosy- Microbiology, including microbial physiology- Molecular epidemiology- Non-tuberculous Mycobacteria- Pathogenesis- Pathology- Vaccine development. This Journal does not accept case-reports. The resurgence of interest in tuberculosis has accelerated the pace of relevant research and Tuberculosis has grown with it, as the only journal dedicated to experimental biomedical research in tuberculosis.