Mycobacterium tuberculosis-macrophage interaction: Molecular updates

Bo, Haotian; Moure, Ulrich Aymard Ekomi; Yang, Yuanmiao; Pan, Jun; Li, Li; Wang, Miao; Ke, Xiaoxue; Cui, Hongjuan

doi:10.3389/fcimb.2023.1062963

Cited by 13 publications

(6 citation statements)

References 154 publications

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“…Macrophages are the main host immune response cells of the body and affect the intracellular growth and persistence of Mtb during all phases of tuberculosis, from primary infection with bacillary dissemination, through latency and reactivation tuberculosis 8 , 9 . Activated macrophages could clear intracellular infected Mtb.…”

Section: Introductionmentioning

confidence: 99%

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circRNA_SLC8A1 promotes the survival of mycobacterium tuberculosis in macrophages by upregulating expression of autophagy-related protein SQSTM1/p62 to activate the NF-κB pathway

Li,

Gao,

Zhang

et al. 2024

Sci Rep

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Macrophages act as the first immune defense line of the host against Mycobacterium tuberculosis (Mtb). A previous study showed that circRNA_SLC8A1 was significantly upregulated in Mtb-infected macrophages, but its regulatory mechanism in anti-tuberculosis infection is unclear. Therefore, this study aimed to investigate the role of circRNA_SLC8A1 in the anti-tuberculosis activity of macrophages. We showed that circRNA_SLC8A1 was upregulated in tuberculosis patients. Moreover, the binding sites of miR-20b-5p on circRNA_SLC8A1 and Sequestosome 1 (SQSTM1/p62) mRNA were predicted by StarBase and verified by the double luciferase reporter gene assay. Next, we found that miR-20b-5p expression was decreased, while SQSTM1 protein expression was increased in a time- and dose-dependent manner in the human macrophage U937 in response to Mtb infection. Furthermore, circRNA_SLC8A1 overexpression vector (circRNA_SLC8A1) or shRNA (sh-circRNA_SLC8A1) and/or miR-20b-5p mimic or inhibitor and/or SQSTM1 overexpression vector (SQSTM1) or small interfering RNA (si-SQSTM1) or its corresponding control were transfected into Mtb-infected macrophages. Results showed that overexpression of circRNA_SLC8A1 or miR-20b-5p inhibitor promoted the secretion of pro-inflammatory factors IL-1β, IL-6, and TNF-α, increased Nitric Oxide (NO) content and inducible nitric oxide synthase (iNOS) expression, inhibited Reactive oxygen species (ROS) production. Cleaved-caspase-3 protein expression, and cell apoptosis, and promoted Mtb survival. Silencing SQSTM1 inhibited secretion of pro-inflammatory factors and activation of the NF-κB pathway. Overexpression of miR‐20b‐5p blocked the promoting of circ‐SLC8A1 on SQSTM1 protein expression. In summary, circRNA_SLC8A1 sponged miR‐20b‐5p to upregulate SQSTM1/p62 expression and promoted Mtb survival in macrophages through the NF-κB signaling pathway.

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Section: Introductionmentioning

confidence: 99%

“…Activated macrophages could clear intracellular infected Mtb. In contrast, Mtb could survive and disseminate by inducing death of infected macrophages 9 , 10 . Bacterial dissemination is enhanced after death of macrophages infected with Mtb.…”

Section: Introductionmentioning

confidence: 99%

circRNA_SLC8A1 promotes the survival of mycobacterium tuberculosis in macrophages by upregulating expression of autophagy-related protein SQSTM1/p62 to activate the NF-κB pathway

Li,

Gao,

Zhang

et al. 2024

Sci Rep

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“…During MTB infection, macrophages interact with pathogens to create a specific immune milieu (Bo et al, 2023). Macrophages are the major host cells for MTB and can polarize into the M1 phenotype, resulting in the production of large amounts of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6) (Cooper et al, 2011).…”

Section: Discussionmentioning

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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“…Indirect detection involves soluble factors such as collectins and complements, which facilitate Mtb internalization by macrophages. Additionally, a variety of PRRs on macrophages identify pathogen-associated molecular patterns (PAMPs) on the cell surfaces and in macrophage phagolysosomes and cytosol ( 39 ). Among membrane-bound receptors, TLR2 and 4 are implicated in the innate immune response to Mtb in the respiratory tract ( 40 ).…”

Section: Tnf: a Contentious Factor During Host-mtb Interaction In Tbmentioning

confidence: 99%

TNF in Human Tuberculosis: A Double-Edged Sword

Yuk,

Kim,

Kim

et al. 2024

Immune Netw

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TNF, a pleiotropic proinflammatory cytokine, is important for protective immunity and immunopathology during Mycobacterium tuberculosis (Mtb) infection, which causes tuberculosis (TB) in humans. TNF is produced primarily by phagocytes in the lungs during the early stages of Mtb infection and performs diverse physiological and pathological functions by binding to its receptors in a context-dependent manner. TNF is essential for granuloma formation, chronic infection prevention, and macrophage recruitment to and activation at the site of infection. In animal models, TNF, in cooperation with chemokines, contributes to the initiation, maintenance, and clearance of mycobacteria in granulomas. Although anti-TNF therapy is effective against immune diseases such as rheumatoid arthritis, it carries the risk of reactivating TB. Furthermore, TNF-associated inflammation contributes to cachexia in patients with TB. This review focuses on the multifaceted role of TNF in the pathogenesis and prevention of TB and underscores the importance of investigating the functions of TNF and its receptors in the establishment of protective immunity against and in the pathology of TB. Such investigations will facilitate the development of therapeutic strategies that target TNF signaling, which makes beneficial and detrimental contributions to the pathogenesis of TB.

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Mycobacterium tuberculosis-macrophage interaction: Molecular updates

Cited by 13 publications

References 154 publications

circRNA_SLC8A1 promotes the survival of mycobacterium tuberculosis in macrophages by upregulating expression of autophagy-related protein SQSTM1/p62 to activate the NF-κB pathway

circRNA_SLC8A1 promotes the survival of mycobacterium tuberculosis in macrophages by upregulating expression of autophagy-related protein SQSTM1/p62 to activate the NF-κB pathway

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

TNF in Human Tuberculosis: A Double-Edged Sword

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