The disease tuberculosis is fatal if untreated. It is caused by the acid‐fast bacilli Mycobacterium tuberculosis. Mycobacterium resides and replicates within the alveolar macrophages, causing inflammation and granuloma, wherein macrophage‐T cell interactions enhance the inflammation‐causing pulmonary caseous lesions. The first interactions between Mycobacterium and the receptors on macrophages decide the fate of Mycobacterium because of phagolysosomal impairments and the expression of several miRNAs, which may regulate CD40 expression on macrophages. While the altered phagolysosomal functions impede antigen presentation to the T cell‐expressed antigen receptor, the interactions between the macrophage‐expressed CD40 and the T cell‐expressed CD40‐ligand (CD40L or CD154) provide signals to T cells and Mycobacterium‐infected macrophages. These two functions significantly influence the resolution or persistence of Mycobacterium infection. CD40 controls T‐cell polarisation and host‐protective immunity by eliciting interleukin‐12p40, nitric oxide, reactive oxygen species and IFN‐γ production. Indeed, CD40‐deficient mice succumb to low‐dose aerosol infection with Mycobacterium because of deficient interleukin (IL)‐12 production leading to impaired IFN‐γ‐secreting T‐cell response. In contrast, despite generating fewer granulomas, the CD40L‐deficient mice developed anti‐mycobacterial T‐cell responses to the levels observed in the wild‐type mice. These host‐protective responses are significantly subdued by the Mycobacterium‐infected macrophage produced TGF‐β and IL‐10, which promote pro‐mycobacterial T‐cell responses. The CD40‐CD40L‐induced counteractive immune responses against Mycobacterium thus present a conundrum that we explain here with a reconciliatory hypothesis. Experimental validation of the hypothesis will provide a rationale for designing anti‐tubercular immunotherapy.

中文翻译：

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分枝杆菌的进行：miRNA截获宿主细胞CD40信号

如果不治疗，结核病是致命的。它是由耐酸杆菌结核分枝杆菌引起的。分枝杆菌在肺泡巨噬细胞中驻留并复制，引起炎症和肉芽肿，其中巨噬细胞-T细胞相互作用增强了引起炎症的肺干酪样病变。分枝杆菌与巨噬细胞受体之间的首次相互作用决定了分枝杆菌的命运由于噬菌体的损伤和一些miRNA的表达，这可能调节巨噬细胞上CD40的表达。尽管吞噬溶酶体功能的改变会阻止抗原呈递给T细胞表达的抗原受体，但巨噬细胞表达的CD40和T细胞表达的CD40配体（CD40L或CD154）之间的相互作用为T细胞和分枝杆菌感染的巨噬细胞提供了信号。这两个功能显着影响分枝杆菌感染的解决或持久性。CD40通过诱导白介素12p40，一氧化氮，活性氧和IFN-γ的产生来控制T细胞极化和宿主保护性免疫。实际上，缺乏CD40的小鼠会因分枝杆菌而导致低剂量气溶胶感染由于白细胞介素（IL）-12产量不足，导致IFN-γ分泌性T细胞反应受损。相比之下，尽管产生的肉芽瘤较少，但CD40L缺陷小鼠对野生型小鼠产生了抗分枝杆菌T细胞反应。这些宿主保护反应被分枝杆菌感染的巨噬细胞产生的TGF-β和IL-10显着减弱，它们促进了分枝杆菌T细胞反应。因此，CD40-CD40L诱导的针对分枝杆菌的抵抗性免疫反应呈现出一个难题，我们在这里以和解假设来解释这一难题。假说的实验验证将为设计抗结核免疫疗法提供理论依据。