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Downregulation of monocyte miRNAs: implications for immune dysfunction and disease severity in drug-resistant tuberculosis
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 th...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10345223/ https://www.ncbi.nlm.nih.gov/pubmed/37457712 http://dx.doi.org/10.3389/fimmu.2023.1197805 |
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author | Sampath, Pavithra Moorthy, Manju Menon, Athul Madhav, Lekshmi Janaki, Aishwarya Dhanapal, Madhavan Natarajan, Alangudi Palaniappan Hissar, Syed Ranganathan, Uma Devi Ramaswamy, Gopalakrishna Bethunaickan, Ramalingam |
author_facet | Sampath, Pavithra Moorthy, Manju Menon, Athul Madhav, Lekshmi Janaki, Aishwarya Dhanapal, Madhavan Natarajan, Alangudi Palaniappan Hissar, Syed Ranganathan, Uma Devi Ramaswamy, Gopalakrishna Bethunaickan, Ramalingam |
author_sort | Sampath, Pavithra |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10345223 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103452232023-07-15 Downregulation of monocyte miRNAs: implications for immune dysfunction and disease severity in drug-resistant tuberculosis Sampath, Pavithra Moorthy, Manju Menon, Athul Madhav, Lekshmi Janaki, Aishwarya Dhanapal, Madhavan Natarajan, Alangudi Palaniappan Hissar, Syed Ranganathan, Uma Devi Ramaswamy, Gopalakrishna Bethunaickan, Ramalingam Front Immunol Immunology 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. Frontiers Media S.A. 2023-06-29 /pmc/articles/PMC10345223/ /pubmed/37457712 http://dx.doi.org/10.3389/fimmu.2023.1197805 Text en Copyright © 2023 Sampath, Moorthy, Menon, Madhav, Janaki, Dhanapal, Natarajan, Hissar, Ranganathan, Ramaswamy and Bethunaickan https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Sampath, Pavithra Moorthy, Manju Menon, Athul Madhav, Lekshmi Janaki, Aishwarya Dhanapal, Madhavan Natarajan, Alangudi Palaniappan Hissar, Syed Ranganathan, Uma Devi Ramaswamy, Gopalakrishna Bethunaickan, Ramalingam Downregulation of monocyte miRNAs: implications for immune dysfunction and disease severity in drug-resistant tuberculosis |
title | Downregulation of monocyte miRNAs: implications for immune dysfunction and disease severity in drug-resistant tuberculosis |
title_full | Downregulation of monocyte miRNAs: implications for immune dysfunction and disease severity in drug-resistant tuberculosis |
title_fullStr | Downregulation of monocyte miRNAs: implications for immune dysfunction and disease severity in drug-resistant tuberculosis |
title_full_unstemmed | Downregulation of monocyte miRNAs: implications for immune dysfunction and disease severity in drug-resistant tuberculosis |
title_short | Downregulation of monocyte miRNAs: implications for immune dysfunction and disease severity in drug-resistant tuberculosis |
title_sort | downregulation of monocyte mirnas: implications for immune dysfunction and disease severity in drug-resistant tuberculosis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10345223/ https://www.ncbi.nlm.nih.gov/pubmed/37457712 http://dx.doi.org/10.3389/fimmu.2023.1197805 |
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