Immune regulation and emerging roles of noncoding RNAs in Mycobacterium tuberculosis infection

Abstract

Tuberculosis, caused by Mycobacterium tuberculosis, engenders an onerous burden on public hygiene. Congenital and adaptive immunity in the human body act as robust defenses against the pathogens. However, in coevolution with humans, this microbe has gained multiple lines of mechanisms to circumvent the immune response to sustain its intracellular persistence and long-term survival inside a host. Moreover, emerging evidence has revealed that this stealthy bacterium can alter the expression of demic noncoding RNAs (ncRNAs), leading to dysregulated biological processes subsequently, which may be the rationale behind the pathogenesis of tuberculosis. Meanwhile, the differential accumulation in clinical samples endows them with the capacity to be indicators in the time of tuberculosis suffering. In this article, we reviewed the nearest insights into the impact of ncRNAs during Mycobacterium tuberculosis infection as realized via immune response modulation and their potential as biomarkers for the diagnosis, drug resistance identification, treatment evaluation, and adverse drug reaction prediction of tuberculosis, aiming to inspire novel and precise therapy development to combat this pathogen in the future.

Identification of important modules and biomarkers in tuberculosis based on WGCNA

“…Approximately three-fourths of ncRNAs are long noncoding RNAs (lncRNAs), which have a length of over 200 nucleotides and tissue/cell-specific expression patterns. Previous research has suggested that lncRNAs are involved in regulating gene expression via interactions with common biological macromolecules, forming a complex network that regulates multiple normal biological and disease processes ( Fathizadeh et al, 2020 ; Liang et al, 2022 ). A number of studies have examined the expression and function of lncRNAs in various diseases based on co-expression analyses ( Liu et al, 2022 ; Wen et al, 2022 ).…”

“…Although there is no commercial assay based on lncRNAs in TB diagnosis, many researches have confirmed that the abnormal expression of lncRNAs are associated with TB occurrence, development and prognosis, and have the potentials as diagnostic, prognostic biomarkers and therapeutic targets in TB ( Chen et al, 2017 ; Zhang et al, 2022 ; Xu et al, 2023 ). However, the expression patterns and pathogenesis of host lncRNAs in TB patients have not yet been fully elucidated, and mechanistic details regarding the regulatory network involving lncRNAs in TB remain unclear ( Chen et al, 2017 ; Agliano et al, 2019 ; Liang et al, 2022 ). Uncovering the expression profile and co-expression relationship between ncRNAs and mRNA in the host could facilitate the development of novel strategies for TB prevention and therapy ( Xia et al, 2023 ).…”

Analysis of the noncoding RNA regulatory networks of H37Rv- and H37Rv△1759c-infected macrophages

“…The increased expression of circAGFG1 in alveolar lavage fluid of ATB patients can inhibit the apoptosis of M. tb-infected macrophages and promote autophagy through the circAGFG1/miR-1257/Notch2 axis ( Shi et al, 2020 ). NcRNAs also have the potential to serve as diagnostic markers, therapeutic targets or therapeutic evaluation indicators for TB ( Davuluri and Chauhan, 2022 ; Hemati et al, 2022 ; Liang et al, 2022 ; Wang L. et al, 2022 ; Wang Q. et al, 2022 ; Zhang et al, 2022 ). Studies found that the upregulated hsa_circ_0001953, hsa_circ_0009024, hsa_circ_051239, hsa_circ_029965 and hsa_circ_404022 and the downregulated hsa_circ_0001380 and hsa_circRNA_103571 in the serum and the downregulated NONHSAT101518.2, NONHSAT067134.2, NONHSAT148822.1, and NONHSAT078957.2 in serum exosomes could be used as potential biomarkers for patients with ATB disease ( Huang et al, 2018 ; Yi et al, 2018 ; Luo et al, 2020 ; Fang et al, 2021 ).…”

Functions of exosomal non-coding RNAs to the infection with Mycobacterium tuberculosis

“…Furthermore, it has been indicated that exosomal non-coding RNAs (ncRNAs) are critical regulators involved in the immune defense of M. tb infection. Exosomal ncRNAs regulate the host to resist M. tb infection by dominating the relevant signaling pathways in the infection process ( 14 ). With the development of sequencing technology, a large number of exosomal ncRNAs have been identified in different biological processes of TB.…”