Identification of a novel role of ESAT-6-dependent miR-155 induction during infection of macrophages with<i>Mycobacterium tuberculosis</i>

Kumar, Ranjeet; Halder, Priyanka; Sahu, Sanjaya Kumar; Kumar, Manish; Kumari, Mandavi; Jana, Kuladip; Ghosh, Zhumur; Sharma, Pawan; Kundu, Manikuntala; Basu, Joyoti

doi:10.1111/j.1462-5822.2012.01827.x

Cited by 143 publications

(130 citation statements)

References 54 publications

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“…However, with some exceptions (17,(30)(31)(32)(33)(34)(35), the majority of these studies have failed to identify downstream effects on the host immune response for the miRNAs detected with altered expression. A major contributing factor to the lack of concrete targets is the use of mixed cell populations or sputum for the identification of differentially expressed miRNAs during M. tuberculosis infection.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosisDecreases Human Macrophage IFN-γ Responsiveness through miR-132 and miR-26a

Rajaram

Lafuse

et al. 2014

The Journal of Immunology

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IFN-γ–activated macrophages play an essential role in controlling intracellular pathogens; however, macrophages also serve as the cellular home for the intracellular pathogen Mycobacterium tuberculosis. Based on previous evidence that M. tuberculosis can modulate host microRNA (miRNA) expression, we examined the miRNA expression profile of M. tuberculosis–infected primary human macrophages. We identified 31 differentially expressed miRNAs in primary human macrophages during M. tuberculosis infection by NanoString and confirmed our findings by quantitative real-time RT-PCR. In addition, we determined a role for two miRNAs upregulated upon M. tuberculosis infection, miR-132 and miR-26a, as negative regulators of transcriptional coactivator p300, a component of the IFN-γ signaling cascade. Knockdown expression of miR-132 and miR-26a increased p300 protein levels and improved transcriptional, translational, and functional responses to IFN-γ in human macrophages. Collectively, these data validate p300 as a target of miR-132 and miR-26a, and demonstrate a mechanism by which M. tuberculosis can limit macrophage responses to IFN-γ by altering host miRNA expression.

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Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosisDecreases Human Macrophage IFN-γ Responsiveness through miR-132 and miR-26a

Rajaram

Lafuse

et al. 2014

The Journal of Immunology

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“…Mir-155 expression is increased by a wide variety of stimuli, such as TLR ligands (16), and has been shown to promote both antimicrobial (17) and antiviral responses of macrophages (18) through the repression of factors antagonistic to the inflammatory response. For example, by repressing the transcripts encoding suppressor of cytokine signaling 1 and Src homology 2 domain-containing inositol 5-phosphatase 1, mir-155 promotes immunity to Staphylococcus aureus (19) and Francisella tularensis (20), respectively, but negatively impacts Mycobacterium tuberculosis infection (21). Mir-155 has also been reported to be integral in the development of IL-17A-producing CD4 ϩ T cells (Th17 cells) (22), mainly in the context of autoimmune inflammation (16,23), but also during gastrointestinal infection with Helicobacter pylori (24).…”

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confidence: 99%

MicroRNA-155 Is Required for Clearance of Streptococcus pneumoniae from the Nasopharynx

et al. 2014

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Pneumonia caused by؉ T-cell responses in vivo, lower IL-17A mRNA levels in the nasopharynx, and a reduced capacity to induce Th17 cell polarization. Given that knockout mice are also limited in the capacity to generate high-titer S. pneumoniae-specific antibodies, we conclude that mir-155 is a critical mediator of the cellular effectors needed to clear primary and secondary S. pneumoniae colonizations.

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“…We also found that miR-125a expression in BMDMs was increased by stimulation with ESAT-6 or an avirulent (H37Ra) M. tuberculosis strain (data not shown). Recent study showed that miR-155 is highly upregulated in RAW264.7 cells and BMDMs in response to M. tuberculosis infection and ESAT-6 stimulation, and it plays a role in the downregulation of BTB and CNC homology 1 and SHIP1 to modulate host innate immune responses (44). Additionally, another study reported that miR-99b is highly upregulated in M. tuberculosis H37Rv-infected dendritic cells and macrophages, and it contributes to the enhancement of intracellular bacterial growth and downregulation of proinflammatory cytokines (45).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-125a Inhibits Autophagy Activation and Antimicrobial Responses during Mycobacterial Infection

Kim

Yuk

Kim

et al. 2015

The Journal of Immunology

126

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MicroRNAs (miRNAs) are small noncoding nucleotides that play critical roles in the regulation of diverse biological functions, including the response of host immune cells. Autophagy plays a key role in activating the antimicrobial host defense against Mycobacterium tuberculosis. Although the pathways associated with autophagy must be tightly regulated at a posttranscriptional level, the contribution of miRNAs and whether they specifically influence the activation of macrophage autophagy during M. tuberculosis infection are largely unknown. In this study, we demonstrate that M. tuberculosis infection of macrophages leads to increased expression of miRNA-125a-3p (miR-125a), which targets UV radiation resistance-associated gene (UVRAG), to inhibit autophagy activation and antimicrobial responses to M. tuberculosis. Forced expression of miR-125a significantly blocked M. tuberculosis–induced activation of autophagy and phagosomal maturation in macrophages, and inhibitors of miR-125a counteracted these effects. Both TLR2 and MyD88 were required for biogenesis of miR-125a during M. tuberculosis infection. Notably, activation of the AMP-activated protein kinase significantly inhibited the expression of miR-125a in M. tuberculosis–infected macrophages. Moreover, either overexpression of miR-125a or silencing of UVRAG significantly attenuated the antimicrobial effects of macrophages against M. tuberculosis. Taken together, these data indicate that miR-125a regulates the innate host defense by inhibiting the activation of autophagy and antimicrobial effects against M. tuberculosis through targeting UVRAG.

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Identification of a novel role of ESAT-6-dependent miR-155 induction during infection of macrophages withMycobacterium tuberculosis

Cited by 143 publications

References 54 publications

Mycobacterium tuberculosisDecreases Human Macrophage IFN-γ Responsiveness through miR-132 and miR-26a

Mycobacterium tuberculosisDecreases Human Macrophage IFN-γ Responsiveness through miR-132 and miR-26a

MicroRNA-155 Is Required for Clearance of Streptococcus pneumoniae from the Nasopharynx

MicroRNA-125a Inhibits Autophagy Activation and Antimicrobial Responses during Mycobacterial Infection

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