Biosciences, College of Health and Life Sciences, Brunel University London, Uxbridge UB8 3PH, United Kingdom.
Immunology and Cell Biology Laboratory, Department of Zoology, Cooch Behar Panchanan Barma University, Cooch Behar, West Bengal, India.
Immunobiology. 2020 May;225(3):151951. doi: 10.1016/j.imbio.2020.151951. Epub 2020 Apr 27.
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, remains a major global health emergency. It is estimated that one third of global population are affected, predominantly with latent granuloma form of the disease. Mtb co-evolved with humans, for its obligatory intra-macrophage phagosome habitat and slow replication, balanced against unique mycobacterial innate immunity, which appears to be highly complex. TB is transmitted via cough aerosol Mtb inhalation. Bovine TB attenuated Bacillus Calmette Guerin (BCG) live vaccine has been in practice for protection of young children from severe disseminated Mtb infection, but not sufficiently for their lungs, as obtained by trials in TB endemic community. To augment BCG vaccine-driven innate and adaptive immunity for neonates and better protection against adult pulmonary TB, a number of BCG pre-vaccination based, subset vaccine candidates have been tested via animal preclinical, followed by safe clinical trials. BCG also enhances innate macrophage trained immunity and memory, through primordial intracellular Toll-like receptors (TLRs) 7 and 9, which recognise distinct mycobacterial molecular pattern signature. This signature is transmitted by TLR signalling via nuclear factor-κB, for activating innate immune transcription and expression of gene profiling in a mycobacterial signature-specific manner. These are epigenetically imprinted in reprogramming of distinct chromatin areas for innate immune memory, to be recalled following lung reinfection. Unique TB innate immunity and its trained memory are considered independent from adaptive immune B and T cells. On the other hand, adaptive immunity is crucial in Mtb containment in granulomatous latency, supported by innate immune cell infiltration. In nearly 5-10 % of susceptible people, latent TB may be activated due to immune evasion by Mtb from intracellular phagosome within macrophage, perpetrating TB. However, BCG and new recombinant BCG vaccines have the capacity, as indicated in pre- and clinical trials, to overcome such Mtb evasion. Various strategies include pro-inflammatory-bactericidal type 1 polarisation (M1) phenotype of the infected macrophage, involving thrombospondin-TLR pathway. Saprophytic M. smegmatis-based recombinant vaccines are also promising candidates against TB. BCG vaccination of neonates/infants in TB endemic countries also reduced their pneumonia caused by various microbes independent of TB immunity. Here, we discuss host immune response against Mtb, its immune evasion strategies, and the important role innate immunity plays in the development of protection against TB.
结核病（TB）是由结核分枝杆菌（Mtb）感染引起的，仍然是全球主要的卫生紧急情况之一。据估计，全球有三分之一的人口受到影响，主要是患有潜伏性肉芽肿形式的疾病。Mtb 与人类共同进化，因为它必须在巨噬细胞内吞噬体中生存，并且复制缓慢，而独特的分枝杆菌先天免疫则与之平衡，这似乎非常复杂。TB 通过咳嗽气溶胶 Mtb 吸入传播。牛型结核分枝杆菌减毒卡介苗（BCG）活疫苗已用于保护幼儿免受严重播散性 Mtb 感染，但对其肺部的保护作用不够，这是在结核病流行社区的试验中获得的。为了增强新生儿对 BCG 疫苗驱动的先天和适应性免疫，并更好地预防成人肺结核，已经通过动物临床前试验测试了许多基于 BCG 疫苗接种的亚单位疫苗候选物，然后进行了安全的临床试验。BCG 还通过原始细胞内 Toll 样受体（TLR）7 和 9 增强先天巨噬细胞训练免疫和记忆，这些受体识别独特的分枝杆菌分子模式特征。该特征通过 TLR 信号转导传递给核因子-κB，用于以分枝杆菌特征特异性方式激活先天免疫转录和基因表达谱。这些特征通过先天免疫记忆的不同染色质区域的重编程进行表观遗传印记，以便在肺部再次感染时被召回。独特的 TB 先天免疫及其训练记忆被认为与适应性免疫 B 和 T 细胞无关。另一方面，适应性免疫对于在肉芽肿潜伏性中控制 Mtb 至关重要，这得益于先天免疫细胞的浸润。在大约 5-10%的易感人群中，由于 Mtb 从巨噬细胞内的吞噬体中逃避免疫，潜伏性 TB 可能被激活，从而导致结核病。然而，正如临床前和临床试验所示，BCG 和新的重组 BCG 疫苗有能力克服这种 Mtb 逃避。各种策略包括感染巨噬细胞的促炎杀菌型 1 极化（M1）表型，涉及血栓素-TLR 途径。基于腐生分枝杆菌的重组疫苗也是对抗结核病的有前途的候选物。在结核病流行国家对新生儿/婴儿进行 BCG 疫苗接种也降低了他们因各种微生物引起的肺炎，而与 TB 免疫无关。在这里，我们讨论宿主对 Mtb 的免疫反应、其免疫逃避策略以及先天免疫在结核病保护中的重要作用。
