Dataset Information

Downregulation of monocyte miRNAs: implications for immune dysfunction and disease severity in drug-resistant tuberculosis.

ABSTRACT:

Background

Monocyte miRNAs govern both protective and pathological responses during tuberculosis (TB) through their differential expression and emerged as potent targets for biomarker discovery and host-directed therapeutics. Thus, this study examined the miRNA profile of sorted monocytes across the TB disease spectrum [drug-resistant TB (DR-TB), drug-sensitive TB (DS-TB), and latent TB] and in healthy individuals (HC) to understand the underlying pathophysiology and their regulatory mechanism.

Methods

We sorted total monocytes including three subsets (HLA-DR⁺CD14⁺, HLA-DR⁺CD14⁺CD16⁺, and HLA-DR⁺CD16⁺cells) from peripheral blood mononuclear cells (PBMCs) of healthy and TB-infected individuals through flow cytometry and subjected them to NanoString-based miRNA profiling.

Results

The outcome was the differential expression of 107 miRNAs particularly the downregulation of miRNAs in the active TB groups (both drug-resistant and drug-sensitive). The miRNA profile revealed differential expression signatures: i) decline of miR-548m in DR-TB alone, ii) decline of miR-486-3p in active TB but significant elevation only in LTB iii) elevation of miR-132-3p only in active TB (DR-TB and DS-TB) and iv) elevation of miR-150-5p in DR-TB alone. The directionality of functions mediated by monocyte miRNAs from Gene Set Enrichment Analysis (GSEA) facilitated two phenomenal findings: i) a bidirectional response between active disease (activation profile in DR-TB and DS-TB compared to LTB and HC) and latent infection (suppression profile in LTB vs HC) and ii) hyper immune activation in the DR-TB group compared to DS-TB.

Conclusion

Thus, monocyte miRNA signatures provide pathological clues for altered monocyte function, drug resistance, and disease severity. Further studies on monocyte miRNAs may shed light on the immune regulatory mechanism for tuberculosis.

SUBMITTER: Sampath P

PROVIDER: S-EPMC10345223 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Downregulation of monocyte miRNAs: implications for immune dysfunction and disease severity in drug-resistant tuberculosis.

Sampath Pavithra P Moorthy Manju M Menon Athul A Madhav Lekshmi L Janaki Aishwarya A Dhanapal Madhavan M Natarajan Alangudi Palaniappan AP Hissar Syed S Ranganathan Uma Devi UD Ramaswamy Gopalakrishna G Bethunaickan Ramalingam R

Frontiers in immunology 20230629

<h4>Background</h4>Monocyte miRNAs govern both protective and pathological responses during tuberculosis (TB) through their differential expression and emerged as potent targets for biomarker discovery and host-directed therapeutics. Thus, this study examined the miRNA profile of sorted monocytes across the TB disease spectrum [drug-resistant TB (DR-TB), drug-sensitive TB (DS-TB), and latent TB] and in healthy individuals (HC) to understand the underlying pathophysiology and their regulatory mec ...[more]

PMID: 37457712

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Project description:BackgroundMulti-drug resistant tuberculosis (MDR TB) is a major health challenge in India that is gaining increasing public attention, but the implications of India's evolving MDR TB epidemic are poorly understood. As India's MDR TB epidemic is transitioning from a treatment-generated to transmission-generated epidemic, we sought to evaluate the potential effectiveness of the following two disease control strategies on reducing the prevalence of MDR TB: a) improving treatment of non-MDR TB; b) shortening the infectious period between the activation of MDR TB and initiation of effective MDR treatment.Methods and findingsWe developed a dynamic transmission microsimulation model of TB in India. The model followed individuals by age, sex, TB status, drug resistance status, and treatment status and was calibrated to Indian demographic and epidemiologic TB time trends. The main effectiveness measure was reduction in the average prevalence reduction of MDR TB over the ten years after control strategy implementation. We find that improving non-MDR cure rates to avoid generating new MDR cases will provide substantial non-MDR TB benefits but will become less effective in reducing MDR TB prevalence over time because more cases will occur from direct transmission--by 2015, the model estimates 42% of new MDR cases are transmission-generated and this proportion continues to rise over time, assuming equal transmissibility of MDR and drug-susceptible TB. Strategies that disrupt MDR transmission by shortening the time between MDR activation and treatment are projected to provide greater reductions in MDR prevalence compared with improving non-MDR treatment quality: implementing MDR diagnostic improvements in 2017 is expected to reduce MDR prevalence by 39%, compared with 11% reduction from improving non-MDR treatment quality.ConclusionsAs transmission-generated MDR TB becomes a larger driver of the MDR TB epidemic in India, rapid and accurate MDR TB diagnosis and treatment will become increasingly effective in reducing MDR TB cases compared to non-MDR TB treatment improvements.

Dataset Information

Downregulation of monocyte miRNAs: implications for immune dysfunction and disease severity in drug-resistant tuberculosis.

Background

Methods

Results

Conclusion

Publications

Downregulation of monocyte miRNAs: implications for immune dysfunction and disease severity in drug-resistant tuberculosis.

Similar Datasets

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