The Macrophage: A Disputed Fortress in the Battle against Mycobacterium tuberculosis.
The Macrophage: A Disputed Fortress in the Battle against Mycobacterium tuberculosis.
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DOI：
10.3389/fmicb.2017.02284
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发表时间：
2017
影响因子：
5.2
通讯作者：
Simeone R
中科院分区：
文献类型：
--
作者：
Queval CJ;Brosch R;Simeone R
结核分枝杆菌（Mycobacterium tuberculosis，Mtb）是人类结核病的病原体，困扰人类数千年。结核病仍然是我们这个时代的一个主要公共卫生问题，每天在全世界造成4,400多人死亡，死亡人数超过艾滋病毒。在吸入结核杆菌污染的气溶胶后，结核病原发感染开始于终末肺气道，在那里结核杆菌被肺泡巨噬细胞吸收。虽然巨噬细胞被称为病原体的专业杀手，但结核分枝杆菌采取了显着的策略来规避宿主防御，建立合适的生存和增殖条件。在巨噬细胞内，结核分枝杆菌最初驻留在吞噬体内，其存活主要取决于其通过抑制吞噬溶酶体生物发生和酸化过程以及通过逐渐进入胞质溶胶来控制吞噬体加工的能力。细菌进入胞质空间是特异性免疫应答和细胞死亡程序的决定因素，这两者都是Mtb复制和传播所需的。了解巨噬细胞内Mtb存活的分子事件对于改进基于疫苗的治疗策略是至关重要的，以帮助宿主在与凶猛的入侵者Mtb的战斗中更好地保护自己。在这篇小型综述中，我们讨论了最近的研究，探索结核分枝杆菌如何征服巨噬细胞并将其转化为生存和传播的战略基地，以及宿主的相关防御策略。
Mycobacterium tuberculosis (Mtb), the etiological agent of human tuberculosis (TB), has plagued humans for thousands of years. TB still remains a major public health problem in our era, causing more than 4,400 deaths worldwide every day and killing more people than HIV. After inhaling Mtb-contaminated aerosols, TB primo-infection starts in the terminal lung airways, where Mtb is taken up by alveolar macrophages. Although macrophages are known as professional killers for pathogens, Mtb has adopted remarkable strategies to circumvent host defenses, building suitable conditions to survive and proliferate. Within macrophages, Mtb initially resides inside phagosomes, where its survival mostly depends on its ability to take control of phagosomal processing, through inhibition of phagolysosome biogenesis and acidification processes, and by progressively getting access to the cytosol. Bacterial access to the cytosolic space is determinant for specific immune responses and cell death programs, both required for the replication and the dissemination of Mtb. Comprehension of the molecular events governing Mtb survival within macrophages is fundamental for the improvement of vaccine-based and therapeutic strategies in order to help the host to better defend itself in the battle against the fierce invader Mtb. In this mini-review, we discuss recent research exploring how Mtb conquers and transforms the macrophage into a strategic base for its survival and dissemination as well as the associated defense strategies mounted by host.