MicroRNA-155, a double-blade sword regulator of innate tuberculosis immunity

Abstract

Tuberculosis (TB) is a chronic, life-threatening disease caused by unusual facultative intracellular bacteria, Mycobacterium tuberculosis. This bacterium has unique resistance to many antimicrobial agents and has become a major global health concern due to emerging multidrug-resistant strains. Additionally, it has developed multiple schemes to exploit host immune signaling and establish long-term survival within host tissues. Thus, understanding the pathways that govern the crosstalk between the bacterium and the immune system could provide a new avenue for therapeutic interventions. MicroRNAs (miRs) are short, noncoding, and regulator RNA molecules that control the expression of cellular genes by targeting their mRNAs post-transcriptionally. MiR-155 is one of the most crucial miR in shaping the host immune defenses against M. tuberculosis. MiR-155 is remarkably downregulated in patients with clear clinical TB symptoms in comparison with latently infected patients and/or healthy individuals, thereby implicating its role in controlling M. tuberculosis infection. However, functional probing of miR-155 suggests dual effects in regulating the host's innate defenses in response to mycobacterial infection. This review provides comprehensive knowledge and future perspectives regarding complex signaling pathways that mediated miR-155 expression during M. tuberculosis infections. Moreover, miR-155-targeting signaling orchestrates inflammatory mediators' production, apoptosis, and autophagy.

Keywords: Apoptosis; Autophagy; Inflammatory; Mycobacterium tuberculosis; miR-155.