Robust lysosomal rewiring in Mtb infected macrophages mediated by Mtb lipids restricts the intracellular bacterial survival

Sachdeva, Kuldeep Singh; Goel, Manisha; Sudhakar, Malvika; Mehta, Mayank R.; Rajmani, Raju S; Raman, Karthik; Singh, Alakesh; Sundaramurthy,

doi:10.1101/845800

Cited by 2 publications

(1 citation statement)

References 70 publications

(113 reference statements)

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“…Macrophages play an important regulatory role in the regulation of tuberculosis. They act as the first line of defense against Mycobacterium tuberculosis, actively phagocytosing and eliminating the pathogen through cytocytosis and lysosomal degradation (Sachdeva et al, 2020). Additionally, macrophages act as antigen-presenting cells, degrading Mycobacterium tuberculosis into immunogenic antigenic polypeptides presented to CD4 + T cells and CD8 + T cells via MHC I and II molecules, triggering an adaptive immune response and activating effector cell killing mechanisms to eliminate the pathogen (Cui et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Differential expression analysis of miRNAs in macrophage-derived exosomes in the tuberculosis-infected bone microenvironment

et al. 2023

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BackgroundMacrophages play an important role in regulating the course of spinal tuberculosis within the bone microenvironment. This study aimed to investigate the differential expression of miRNA in macrophage-derived exosomes within the tuberculosis-infected bone microenvironment, to identify miRNAs that hold potential as diagnostic markers and therapeutic targets.MethodsWe established study cohorts for spinal tuberculosis, collected bone marrow blood samples, isolated macrophage exosomes, and performed exosome miRNA sequencing. A miRNA-mRNA co-expression network was constructed using WGCNA analysis. Gene GO analysis and KEGG pathway enrichment analysis were performed using KOBAS software. Target miRNAs were selected based on fold change, P-value, and false discovery rate, and their validation was carried out using qRT-PCR and ROC curve studies. Subsequently, we constructed a target gene network for these miRNAs and performed KEGG pathway enrichment analysis to explore the potential signaling mechanisms involved in regulating the disease course of spinal tuberculosis.ResultsOur findings revealed that macrophages from the tuberculosis-infected bone microenvironment exhibited an M1 phenotype. The successful extraction of exosomes from macrophage supernatants was confirmed through electron microscopy, particle size analysis, and protein blot analysis. Exosome miRNA-seq demonstrated that 28 miRNAs were up-regulated, while 34 miRNAs were down-regulated in individuals with spinal tuberculosis. GO analysis and KEGG pathway enrichment analysis indicated that the differentially expressed miRNAs were involved in various biological processes, cell components, molecular functions, and signaling pathways, which collectively contribute to the regulation of the disease course of spinal tuberculosis. Notably, miRNA-125b-5p was successfully selected based on fold change, p-value, and false discovery rate. qRT-PCR validation further confirmed the significant up-regulation of miRNA-125b-5p in spinal tuberculosis. The ROC curve revealed that miR-125b-5p is a potential diagnostic biomarker for spinal tuberculosis. Moreover, construction of the miRNA-125b-5p target gene network and subsequent KEGG enrichment analysis highlighted the importance of MAPK, TNF, Ras, Rap1, and the PI3K-Akt signaling pathways in the regulation of the disease course of spinal tuberculosis.ConclusionOur study demonstrates differential expression of miRNAs in macrophage-derived exosomes in the tuberculosis-infected bone microenvironment. Specifically, MiRNA-125b-5p is significantly up-regulated in spinal tuberculosis and shows potential as a diagnostic biomarker for spinal tuberculosis.

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Section: Introductionmentioning

confidence: 99%

Differential expression analysis of miRNAs in macrophage-derived exosomes in the tuberculosis-infected bone microenvironment

et al. 2023

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Meeting report – the Microtubules, Motors, Transport and Trafficking (M2T2) 2019 meeting

Parton

Mylavarapu

2020

Journal of Cell Science

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The Molecular Motors, Transport and Trafficking (M2T2) meeting serves as a platform for both Indian and global scientists working on the cytoskeleton, cytoskeletal motors and membrane trafficking to gather and discuss the latest developments in the field. The 2019 edition of the meeting, held from 18-20 October at the National Brain Research Centre (NBRC), Manesar, India and organised by Mahak Sharma (Indian Institute of Science Education and Research, Mohali) and Anindya Ghosh Roy (NBRC), was witness to stimulating research on a range of topics related to the cytoskeleton, including cytoskeletal organization, motor protein function and regulation, mechanical forces and vesicular transport, and trafficking in health and disease.

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Robust lysosomal rewiring in Mtb infected macrophages mediated by Mtb lipids restricts the intracellular bacterial survival

Abstract: 17

Cited by 2 publications

References 70 publications

Differential expression analysis of miRNAs in macrophage-derived exosomes in the tuberculosis-infected bone microenvironment

Differential expression analysis of miRNAs in macrophage-derived exosomes in the tuberculosis-infected bone microenvironment

Meeting report – the Microtubules, Motors, Transport and Trafficking (M2T2) 2019 meeting

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