Laboratório de Bioquímica de Resposta ao Estresse, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Laboratório de Microbiologia Celular, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Immunol Rev. 2021 May;301(1):193-208. doi: 10.1111/imr.12962. Epub 2021 Apr 28.
Leprosy is a much-feared incapacitating infectious disease caused by Mycobacterium leprae or M lepromatosis, annually affecting roughly 200,000 people worldwide. During host-pathogen interaction, M leprae subverts the immune response, leading to development of disease. Throughout the last few decades, the impact of energy metabolism on the control of intracellular pathogens and leukocytic differentiation has become more evident. Mitochondria play a key role in regulating newly-discovered immune signaling pathways by controlling redox metabolism and the flow of energy besides activating inflammasome, xenophagy, and apoptosis. Likewise, this organelle, whose origin is probably an alphaproteobacterium, directly controls the intracellular pathogens attempting to invade its niche, a feature conquered at the expense of billions of years of coevolution. In the present review, we discuss the role of reduced host cell mitochondrial activity during M leprae infection and the consequential fates of M leprae and host innate immunity. Conceivably, inhibition of mitochondrial energy metabolism emerges as an overlooked and novel mechanism developed by M leprae to evade xenophagy and the host immune response.
麻风病是一种令人恐惧的使人丧失能力的传染病，由麻风分枝杆菌或麻风分枝杆菌引起，每年在全球影响约 20 万人。在宿主-病原体相互作用过程中，麻风分枝杆菌颠覆了免疫反应，导致疾病的发生。在过去的几十年中，能量代谢对控制细胞内病原体和白细胞分化的影响变得更加明显。线粒体通过控制氧化还原代谢和能量流动，除了激活炎症小体、异噬作用和细胞凋亡外，在调节新发现的免疫信号通路方面发挥着关键作用。同样，这个起源可能是α变形菌的细胞器，直接控制着试图侵入其生态位的细胞内病原体，这一特性是在数十亿年的共同进化过程中牺牲的。在本综述中，我们讨论了麻风分枝杆菌感染过程中宿主细胞线粒体活性降低的作用，以及麻风分枝杆菌和宿主固有免疫的后果。可以想象，抑制线粒体能量代谢可能是麻风分枝杆菌逃避异噬作用和宿主免疫反应的一种被忽视的新机制。
