The Roles of Host Noncoding RNAs in Mycobacterium tuberculosis Infection

Li, Wei; Liu, Kai; Jia, Qingzhi; Zhang, Hui; Bie, Qingli; Zhang, Bin

doi:10.3389/fimmu.2021.664787

Cited by 20 publications

(11 citation statements)

References 118 publications

(147 reference statements)

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“…Tuberculosis (TB) is a global infectious disease caused by a latent infection of the Mycobacterium tuberculosis (MTB) that attacks the host's immune system in an attempt to activate the infection, a disease caused by the bacterium. According to the World Health Organization (WHO), approximately 1.5 million people died from TB in 2018 [ 1 ]. Despite the continuous advances in medical technology and the development of vaccines, the morbidity of TB has not been significantly improved, posing a serious threat to human life and health [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Rifampicin Loaded by HPMA-PLA Nanopolymer on Macrophages Infected with Mycobacterium Tuberculosis

Wang

Liu

et al. 2022

Computational and Mathematical Methods in Medicine

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Purpose. This research was designed to investigate the protective effect of rifampicin (RIF) loaded by N-(2-hydroxypropyl) methylacrylamide- (HPMA-) polylactic acid (PLA) nanopolymer on macrophages infected with Mycobacterium tuberculosis (MTB). Methods. We first induced H37Rv to infect macrophages to build a cell model. Then, the HPMA-PLA nanopolymer loaded with RIF was prepared to treat MTB-infected macrophages. The macrophage activity was tested by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the nitric oxide (NO) in cells was measured through Griess reagent, and the bacterial activity of MTB was observed via the colony-forming unit (CFU) assay. The inflammation-related factors in cells were detected via the enzyme-linked immunosorbent assay (ELISA), the apoptosis of macrophages was examined via flow cytometry, and the expression of apoptosis-related proteins was determined by western blot (WB). Results. HPMA-PLA had no obvious toxicity to macrophages. The expression of NO and inflammatory factors in macrophages infected with MTB increased significantly, but the apoptosis rate was not significantly different from that of uninfected cells. However, after treatment with HPMA-PLA-RIF or free RIF, the inflammatory reaction of infected cells was inhibited, the expression of NO was decreased, the apoptosis rate was increased, and the bacterial activity in cells was decreased, with statistically significant differences; moreover, HPMA-PLA-RIF was more effective than free RIF. Conclusions. HPMA-PLA-RIF has a high protective effect on macrophages infected with MTB, with high safety. Its protective mechanism is at least partly through inhibiting the production of NO and inflammatory response, which can inhibit bacterial activity and induce cell apoptosis.

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Section: Introductionmentioning

confidence: 99%

Protective Effect of Rifampicin Loaded by HPMA-PLA Nanopolymer on Macrophages Infected with Mycobacterium Tuberculosis

Wang

Liu

et al. 2022

Computational and Mathematical Methods in Medicine

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“…Then we found that the expression of NEAT1 was down-regulated in BM cells of both BCG and rBCG-DisA immunized mice, but up-regulated significantly in the organs of rBCG-DisA immunized mice after M. tuberculosis challenge ( Figures 3C–E ). A growing body of research has revealed abnormally expressed lncRNAs in macrophages of TB patients ( 57 ). Thus, these lncRNAs that screened in this study may play roles in the regulation of the trained immunity, which should be investigated further.…”

Section: Discussionmentioning

confidence: 99%

Cyclic di-AMP as endogenous adjuvant enhanced BCG-induced trained immunity and protection against Mycobacterium tuberculosis in mice

Ning

Kang

et al. 2022

Front. Immunol.

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Bacillus Calmette-Guérin (BCG) is a licensed prophylactic vaccine against tuberculosis (TB). Current TB vaccine efforts focus on improving BCG effects through recombination or genetic attenuation and/or boost with different vaccines. Recent years, it was revealed that BCG could elicit non-specific heterogeneous protection against other pathogens such as viruses through a process termed trained immunity. Previously, we constructed a recombinant BCG (rBCG-DisA) with elevated c-di-AMP as endogenous adjuvant by overexpressing di-adenylate cyclase of Mycobacterium tuberculosis DisA, and found that rBCG-DisA induced enhanced immune responses by subcutaneous route in mice after M. tuberculosis infection. In this study, splenocytes from rBCG-DisA immunized mice by intravenous route (i.v) elicited greater proinflammatory cytokine responses to homologous and heterologous re-stimulations than BCG. After M. tuberculosis infection, rBCG-DisA immunized mice showed hallmark responses of trained immunity including potent proinflammatory cytokine responses, enhanced epigenetic changes, altered lncRNA expressions and metabolic rewiring in bone marrow cells and other tissues. Moreover, rBCG-DisA immunization induced higher levels of antibodies and T cells responses in the lung and spleen of mice after M. tuberculosis infection. It was found that rBCG-DisA resided longer than BCG in the lung of M. tuberculosis infected mice implying prolonged duration of vaccine efficacy. Then, we found that rBCG-DisA boosting could prolong survival of BCG-primed mice over 90 weeks against M. tuberculosis infection. Our findings provided in vivo experimental evidence that rBCG-DisA with c-di-AMP as endogenous adjuvant induced enhanced trained immunity and adaptive immunity. What’s more, rBCG-DisA showed promising potential in prime-boost strategy against M. tuberculosis infection in adults.

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“…Different expression patterns of lncRNAs are emerging as critical regulators to control the function of innate and adaptive immune cell types and initiate effective defense mechanisms in TB ( Figure 2 and Table 1 ; Chen Y. G. et al, 2017 ; Wei et al, 2021 ).…”

Section: The Role Of Long Non-coding Rnas In Anti-tuberculosis Immunitymentioning

confidence: 99%

“…In addition, tissue-specific and condition-specific expression patterns suggest that lncRNAs provide potential biomarkers ( Statello et al, 2021 ). Therefore, in-depth elucidation of the effect and mechanism of lncRNAs may develop clinical prospects for precise TB diagnosis and treatments ( Lyu et al, 2021 ; Wei et al, 2021 ). In this paper, we review the progress of lncRNA roles in Mtb infection from host immunity to biomarkers and discuss its potential in clinical diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Long Non-coding RNAs in Tuberculosis: From Immunity to Biomarkers

Zhang

Chen

2022

Front. Microbiol.

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Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is the leading lethal infectious disease with 1.3 million deaths in 2020. Despite significant advances have been made in detection techniques and therapeutic approaches for tuberculosis, no suitable diagnostic tools are available for early and precise screening. Many studies have reported that Long non-coding RNAs (lncRNAs) play a regulatory role in gene expression in the host immune response against Mtb. Dysregulation of lncRNAs expression patterns associated with immunoregulatory pathways arose in mycobacterial infection. Meanwhile, host-induced lncRNAs regulate antibacterial processes such as apoptosis and autophagy to limit bacterial proliferation. In this review, we try to summarize the latest reports on how dysregulated expressed lncRNAs influence host immune response in tuberculosis infection. We also discuss their potential clinical prospects for tuberculosis diagnosis and development as molecular biomarkers.

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The Roles of Host Noncoding RNAs in Mycobacterium tuberculosis Infection

Cited by 20 publications

References 118 publications

Protective Effect of Rifampicin Loaded by HPMA-PLA Nanopolymer on Macrophages Infected with Mycobacterium Tuberculosis

Protective Effect of Rifampicin Loaded by HPMA-PLA Nanopolymer on Macrophages Infected with Mycobacterium Tuberculosis

Cyclic di-AMP as endogenous adjuvant enhanced BCG-induced trained immunity and protection against Mycobacterium tuberculosis in mice

Long Non-coding RNAs in Tuberculosis: From Immunity to Biomarkers

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