Mycobacterium tuberculosis controls microRNA-99b (miR-99b) Expression in infected murine dendritic cells to modulate host immunity

Singh, Yogesh ; Kaul, Vandana ; Mehra, Alka ; Chatterjee, Samit ; Tousif, Sultan ; Dwivedi, Ved Prakash ; Suar, Mrutyunjay ; Van Kaer, Luc ; Bishai, William R. ; Das, Gobardhan (2013) Mycobacterium tuberculosis controls microRNA-99b (miR-99b) Expression in infected murine dendritic cells to modulate host immunity Journal of Biological Chemistry, 288 (7). pp. 5056-5061. ISSN 0021-9258

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Official URL: http://www.jbc.org/content/288/7/5056.full

Related URL: http://dx.doi.org/10.1074/jbc.C112.439778

Abstract

Mycobacterium tuberculosis resides and replicates within host phagocytes by modulating host microbicidal responses. In addition, it suppresses the production of host protective cytokines to prevent activation of and antigen presentation by M. tuberculosis-infected cells, causing dysregulation of host protective adaptive immune responses. Many cytokines are regulated by microRNAs (miRNAs), a newly discovered class of small noncoding RNAs, which have been implicated in modulating host immune responses in many bacterial and viral diseases. Here, we show that miRNA-99b (miR-99b), an orphan miRNA, plays a key role in the pathogenesis of M. tuberculosis infection. We found that miR-99b expression was highly up-regulated in M. tuberculosis strain H37Rv-infected dendritic cells (DCs) and macrophages. Blockade of miR-99b expression by antagomirs resulted in significantly reduced bacterial growth in DCs. Interestingly, knockdown of miR-99b in DCs significantly up-regulated proinflammatory cytokines such as IL-6, IL-12, and IL-1β. Furthermore, mRNA and membrane-bound protein data indicated that inhibition of miR-99b augments TNF-α and TNFRSF-4 production. Thus, miR-99b targets TNF-α and TNFRSF-4 receptor genes. Treatment of anti-miR-99b-transfected DCs with anti-TNF-α antibody resulted in increased bacterial burden. Thus, our findings unveil a novel host evasion mechanism adopted by M. tuberculosis via miR-99b, which may open up new avenues for designing miRNA-based vaccines and therapies.

Item Type:Article
Source:Copyright of this article belongs to American Society for Biochemistry and Molecular Biology.
Keywords:Innate Immunity; MicroRNA; Mycobacterium Tuberculosis; T Cell; Tumor Necrosis Factor (TNF); DCs
ID Code:112924
Deposited On:07 Jun 2018 05:01
Last Modified:07 Jun 2018 05:01

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