International Centre for Genetic Engineering and Biotechnology, Cape Town Component, Cape Town, South Africa.
Department of Pathology, University of Cape Town, Institute of Infectious Diseases and Molecular Medicine (IDM), Division of Immunology and South African Medical Research Council (SAMRC) Immunology of Infectious Diseases, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Front Immunol. 2021 Oct 20;12:733853. doi: 10.3389/fimmu.2021.733853. eCollection 2021.
Globally, more than 10 million people developed active tuberculosis (TB), with 1.4 million deaths in 2020. In addition, the emergence of drug-resistant strains in many regions of the world threatens national TB control programs. This requires an understanding of host-pathogen interactions and finding novel treatments including host-directed therapies (HDTs) is of utter importance to tackle the TB epidemic. (Mtb), the causative agent for TB, mainly infects the lungs causing inflammatory processes leading to immune activation and the development and formation of granulomas. During TB disease progression, the mononuclear inflammatory cell infiltrates which form the central structure of granulomas undergo cellular changes to form epithelioid cells, multinucleated giant cells and foamy macrophages. Granulomas further contain neutrophils, NK cells, dendritic cells and an outer layer composed of T and B lymphocytes and fibroblasts. This complex granulomatous host response can be modulated by Mtb to induce pathological changes damaging host lung tissues ultimately benefiting the persistence and survival of Mtb within host macrophages. The development of cavities is likely to enhance inter-host transmission and caseum could facilitate the dissemination of Mtb to other organs inducing disease progression. This review explores host targets and molecular pathways in the inflammatory granuloma host immune response that may be beneficial as target candidates for HDTs against TB.
全球范围内，有超过 1000 万人患有活动性肺结核（TB），2020 年有 140 万人因此死亡。此外，世界许多地区出现耐药菌株，这对国家结核病控制规划构成威胁。这就需要了解宿主-病原体相互作用，并找到新的治疗方法，包括宿主定向治疗（HDTs），这对于应对结核病流行至关重要。
分枝杆菌（Mtb）是结核病的病原体，主要感染肺部，引起炎症反应，导致免疫激活和肉芽肿的形成和发展。在结核病进展过程中，形成肉芽肿中央结构的单核炎性细胞浸润会发生细胞变化，形成上皮样细胞、多核巨细胞和泡沫状巨噬细胞。肉芽肿还包含中性粒细胞、NK 细胞、树突状细胞以及由 T 和 B 淋巴细胞和成纤维细胞组成的外层。这种复杂的肉芽肿宿主反应可以被 Mtb 调节，导致宿主肺组织的病理性变化，最终有利于 Mtb 在宿主巨噬细胞中的持续存在和存活。空洞的形成可能会增强宿主间的传播，干酪样物质可能会促进 Mtb 向其他器官的传播，从而导致疾病的进展。本综述探讨了炎症性肉芽肿宿主免疫反应中的宿主靶标和分子途径，这些靶标和途径可能作为针对结核病的 HDTs 的候选靶标有益。
