Tuberculosis-Associated MicroRNAs: From Pathogenesis to Disease Biomarkers

Abstract

Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the most lethal infectious diseases with estimates of approximately 1.4 million human deaths in 2018. M. tuberculosis has a well-established ability to circumvent the host immune system to ensure its intracellular survival and persistence in the host. Mechanisms include subversion of expression of key microRNAs (miRNAs) involved in the regulation of host innate and adaptive immune response against M. tuberculosis. Several studies have reported differential expression of miRNAs during active TB and latent tuberculosis infection (LTBI), suggesting their potential use as biomarkers of disease progression and response to anti-TB therapy. This review focused on the miRNAs involved in TB pathogenesis and on the mechanism through which miRNAs induced during TB modulate cell antimicrobial responses. An attentive study of the recent literature identifies a group of miRNAs, which are differentially expressed in active TB vs. LTBI or vs. treated TB and can be proposed as candidate biomarkers.

Keywords: apoptosis; autophagy; biomarker; diagnosis; disease progression; innate immunity; latent infection; microRNA; pathogenesis; response to therapy; tuberculosis.

Figure 1

Tuberculosis pathogenesis and disease progression. Mycobacterium tuberculosis infection initiates with inhalation of droplets that carry bacteria and their uptake by alveolar macrophages. Innate immune responses characterize the initial phase of infection, with recruitment of inflammatory cells in the lung. Bacterial dissemination to the draining lymph node leads to T cell priming and expansion of antigen-specific T cells. Recruitment of activated macrophages, neutrophils, T cells, and B cells in the lung leads to granuloma formation, which contains M. tuberculosis in a latent status. However, in about 10% of infected individuals, M. tuberculosis escapes immune control and granulomas are disrupted, with release of infectious bacteria.

Figure 2

Graphical representation of miRNA regulation of host immune responses against M. tuberculosis infection. MicroRNAs that are up-regulated or down-regulated during M. tuberculosis infection are indicated with red and green arrows, respectively.

Figure 3

Graphical representation of circulating miRNAs, which are significantly up-regulated (red arrow) or down-regulated (green arrow) in subjects with latent tuberculosis (TB) infection, active TB, or who responded to anti-TB therapy, and have been proposed as candidate biomarkers.