The ESX-1 Virulence Factors Downregulate miR-147-3p in Mycobacterium marinum-Infected Macrophages

Zuo, Xiao-Shu; Wang, Lin; Bao, Yanqing; Sun, Jianjun

doi:10.1128/iai.00088-20

Cited by 16 publications

(10 citation statements)

References 77 publications

(93 reference statements)

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“…The upregulation of miRNA155 inhibits autophagy, which favors Mtb survival in mouse macrophages and human dendritic cells [ 143 , 145 ]. Either the purified EsxA or Mm infection downregulate miR-148 or miR-147 in mouse macrophages, which increases Mm intracellular survival, suggesting that EsxA increases Mm intracellular survival by inhibiting the two miRNAs [ 146 , 147 ].…”

Section: Current Understanding Of Esxa’s Role In Mycobacterium–host Interactionmentioning

confidence: 99%

A Small Protein but with Diverse Roles: A Review of EsxA in Mycobacterium–Host Interaction

Bao

Wang

Sun

2021

Cells

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As a major effector of the ESX-1 secretion system, EsxA is essential for the virulence of pathogenic mycobacteria, such as Mycobacterium tuberculosis (Mtb) and Mycobacterium marinum (Mm). EsxA possesses an acidic pH-dependent membrane permeabilizing activity and plays an essential role by mediating mycobacterial escape from the phagosome and translocation to the cytosol for intracellular replication. Moreover, EsxA regulates host immune responses as a potent T-cell antigen and a strong immunoregulator. EsxA interacts with multiple cellular proteins and stimulates several signal pathways, such as necrosis, apoptosis, autophagy, and antigen presentation. Interestingly, there is a co-dependency in the expression and secretion of EsxA and other mycobacterial factors, which greatly increases the complexity of dissecting the precise roles of EsxA and other factors in mycobacterium–host interaction. In this review, we summarize the current understandings of the roles and functions of EsxA in mycobacterial infection and discuss the challenges and future directions.

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Section: Current Understanding Of Esxa’s Role In Mycobacterium–host Interactionmentioning

confidence: 99%

A Small Protein but with Diverse Roles: A Review of EsxA in Mycobacterium–Host Interaction

Bao

Wang

Sun

2021

Cells

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“…For instance, a study from Liu et al demonstrated that miR-147 overexpression in macrophages could dampen TLR activation-induced cytokine production in vitro [26]. Furthermore, a recent study demonstrated that virulent factor from the Mycobacterium marinum downregulated miR-147 levels and overexpression of miR-147 dampened Mycobacterium marinum-induced cytokine production in murine macrophage cell lines in vitro [28]. These studies imply the functional role of miR-147 during infection and inflammatory stimulations in macrophages, and potentially other myeloid cell populations.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have suggested the functional role of miR-147 in many physiological processes including cell cycle regulation and metabolism [25][26][27][28][29][30][31][32]. Here, the expression pattern of miR-147 across different cells and organs is investigated by RT-qPCR.…”

Section: Mir-147 Expression In Different Cell Lines Primary Cells Amentioning

confidence: 99%

“…MiR-147 (hsa-miR-147b or mmu-miR-147-3p) is located at chromosome 15 in humans and chromosome 2 in mouse. It has been continuously gaining attention as a key regulator of cell cycle progression and inflammatory responses by in vitro and pharmacological studies in vivo [25][26][27][28][29][30][31][32]. For example, miR-147 has been identified as the top upregulated microRNA in lung cancer cells that are tolerant to epidermal growth factor receptor inhibitor, and it orchestrates the metabolic shift of cancer cells for drug tolerance [25].…”

Section: Introductionmentioning

confidence: 99%

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Characterization of a Murine Model System to Study MicroRNA-147 During Inflammatory Organ Injury

et al. 2021

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Inflammatory organ injury and sepsis have profound impacts on the morbidity and mortality of surgical and critical care patients. MicroRNAs are small RNAs composed of 20-25 nucleotides that have a significant contribution to gene regulation. MicroRNA-147 (miR-147), in particular, has been shown to have an emerging role in different physiological functions such as cell cycle regulation and inflammatory responses. However, animal model systems to study tissue-specific functions of miR-147 during inflammatory conditions in vivo are lacking. In the present study, we characterize miR-147 expression in different organs and cell types. Next, we generated a transgenic mouse line with a floxed miR-147 gene. Subsequently, we used this mouse line to generate mice with whole-body deletion of miR-147 (miR-147 −/−) by crossing "floxed" miR-147 mice with transgenic mice expressing Cre recombinase in all tissues (CMVcre mice). Systematic analysis of miR-147 −/− mice demonstrates normal growth, development, and offspring. In addition, deletion of the target gene in different organs was successful at baseline or during inflammation, including the heart, intestine, stomach, liver, spleen, bone marrow, lungs, kidneys, or stomach. Moreover, miR-147 −/− mice have identical baseline inflammatory gene expression compared to C57BL/6 mice, except elevated IL-6 expression in the spleen (7.5 fold, p < 0.05). Taken together, our data show the successful development of a transgenic animal model for tissue and cell-specific deletion of miR-147 that can be used to study the functional roles of miR-147 during inflammatory organ injury.

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“…miR-147-3p expression is modulated by the ESAT-6 secretion system-1 (ESX-1) to mediate the secretion of VFs [ 69 ]. A previous study has shown that the secretion of VFs was mediated by ESX-1, which can aid M. tuberculosis to penetrate the phagosome membrane and translocate into the cytoplasm [ 70 ].…”

Section: Introductionmentioning

confidence: 99%

The current landscape of microRNAs (miRNAs) in bacterial pneumonia: opportunities and challenges

2022

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MicroRNAs (miRNAs), which were initially discovered in Caenorhabditis elegans, can regulate gene expression by recognizing cognate sequences and interfering with the transcriptional or translational machinery. The application of bioinformatics tools for structural analysis and target prediction has largely driven the investigation of certain miRNAs. Notably, it has been found that certain miRNAs which are widely involved in the inflammatory response and immune regulation are closely associated with the occurrence, development, and outcome of bacterial pneumonia. It has been shown that certain miRNA techniques can be used to identify related targets and explore associated signal transduction pathways. This enhances the understanding of bacterial pneumonia, notably for “refractory” or drug-resistant bacterial pneumonia. Although these miRNA-based methods may provide a basis for the clinical diagnosis and treatment of this disease, they still face various challenges, such as low sensitivity, poor specificity, low silencing efficiency, off-target effects, and toxic reactions. The opportunities and challenges of these methods have been completely reviewed, notably in bacterial pneumonia. With the continuous improvement of the current technology, the miRNA-based methods may surmount the aforementioned limitations, providing promising support for the clinical diagnosis and treatment of “refractory” or drug-resistant bacterial pneumonia.

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The ESX-1 Virulence Factors Downregulate miR-147-3p in Mycobacterium marinum-Infected Macrophages

Cited by 16 publications

References 77 publications

A Small Protein but with Diverse Roles: A Review of EsxA in Mycobacterium–Host Interaction

A Small Protein but with Diverse Roles: A Review of EsxA in Mycobacterium–Host Interaction

Characterization of a Murine Model System to Study MicroRNA-147 During Inflammatory Organ Injury

The current landscape of microRNAs (miRNAs) in bacterial pneumonia: opportunities and challenges

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