Chauhan, P and Dandapat, J and Sarkar, A and Saha, B (2020) March of Mycobacterium:miRNAs intercept host cell CD40 signalling. Clinical and Translational Immunology, 9 (10). e1179. ISSN 2020 Oct7;9(10):e1179.

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Abstract

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.

Item Type:	Article
Subjects:	Infection and Immunity
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	18 Apr 2021 13:22
Last Modified:	18 Apr 2021 13:22
URI:	http://nccs.sciencecentral.in/id/eprint/912

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