MicroRNA mediated regulation of immunity against gram-negative bacteria

Keck, Jonathon; Gupta, Rishein; Christenson, Lane K.; Arulanandam, Bernard P.

doi:10.1080/08830185.2017.1347649

Cited by 13 publications

(13 citation statements)

References 179 publications

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“…MicroRNAs play important role in the regulation of immune response to different infectious agents ( 10 ). B. abortus is a facultative intracellular bacterium that can adapt to environmental stressor and replicates in phagocytic cells.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, we and others demonstrated that B. abortus could modulate the immune response through induction of regulatory cytokines such as IL-10 as negative regulation of pro-inflammatory cytokines, suggesting that this interplay between immune responses enables B. abortus persistence in the host ( 7 – 9 ). Recently, studies have increasingly reported the involvement of microRNAs (miRNAs) in the regulation of host responses to bacterial pathogens ( 10 ). miRNAs are small non-coding RNAs that negatively regulate gene expression by directly binding to the 3′ untranslated region (3′ UTR) of their mRNA targets.…”

Section: Introductionmentioning

confidence: 99%

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miR-181a-5p Regulates TNF-α and miR-21a-5p Influences Gualynate-Binding Protein 5 and IL-10 Expression in Macrophages Affecting Host Control of Brucella abortus Infection

et al. 2018

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Brucella abortus is a Gram-negative intracellular bacterium that causes a worldwide zoonosis termed brucellosis, which is characterized as a debilitating infection with serious clinical manifestations leading to severe complications. In spite of great advances in studies involving host–B. abortus interactions, there are many gaps related to B. abortus modulation of the host immune response through regulatory mechanisms. Here, we deep sequenced small RNAs from bone marrow-derived macrophages infected with B. abortus, identifying 69 microRNAs (miRNAs) that were differentially expressed during infection. We further validated the expression of four upregulated and five downregulated miRNAs during infection in vitro that displayed the same profile in spleens from infected mice at 1, 3, or 6 days post-infection. Among these miRNAs, mmu-miR-181a-5p (upregulated) or mmu-miR-21a-5p (downregulated) were selected for further analysis. First, we determined that changes in the expression of both miRNAs induced by infection were dependent on the adaptor molecule MyD88. Furthermore, evaluating putative targets of mmu-miR-181a-5p, we demonstrated this miRNA negatively regulates TNF-α expression following Brucella infection. By contrast, miR-21a-5p targets included a negative regulator of IL-10, programmed cell death protein 4, and several guanylate-binding proteins (GBPs). As a result, during infection, miR-21a-5p led to upregulation of IL-10 expression and downregulation of GBP5 in macrophages infected with Brucella. Since GBP5 and IL-10 are important molecules involved in host control of Brucella infection, we decided to investigate the role of mmu-miR-21a-5p in bacterial replication in macrophages. We observed that treating macrophages with a mmu-miR-21a-5p mimic enhanced bacterial growth, whereas transfection of its inhibitor reduced Brucella load in macrophages. Taken together, the results indicate that downregulation of mmu-miR-21a-5p induced by infection increases GBP5 levels and decreases IL-10 expression thus contributing to bacterial control in host cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

miR-181a-5p Regulates TNF-α and miR-21a-5p Influences Gualynate-Binding Protein 5 and IL-10 Expression in Macrophages Affecting Host Control of Brucella abortus Infection

et al. 2018

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“…MiRNAs (microRNAs) are noncoding small RNA molecules capable of regulating gene expression at the post-transcriptional level [16]. Some host miRNAs have been reported to involve in the host-bacteria crosstalk [17,18], and miRNAs play important roles in modulating macrophages response toward pathogens, e.g. dynamic regulators of macrophage polarization and plasticity [19,20].…”

Section: Introductionmentioning

confidence: 99%

Transcription elements AREB6 and miR-34a affect apoptosis of PAMs by regulating the expression of SS2-related gene PPP1R11

Liu

Qiao

et al. 2019

Cell Cycle

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In our previous work, gene PPP1R11 (protein phosphatase 1 regulatory subunit 11) was significantly expressed in pigs after Streptococcus suis 2 (SS2) challenged. This study firstly confirmed that SS2 induced significant expression of PPP1R11 gene in porcine alveolar macrophage (PAM) cells, and apoptosis of PAM cells were observed. After that, the core promoter of porcine PPP1R11 was identified and its transcription factor AREB6 which significantly regulated PPP1R11. We also characterized that the PPP1R11 gene is a target of miR-34a. Further, we found that PPP1R11 helped to inhibit apoptosis of PAM cells under SS2 infecting, through transcription factor AREB6 was negatively correlated with apoptosis whereas miR-34a was positively correlated. Those findings provide a functional connection among the transcription factor AREB6, miR-34a, PPP1R11 gene and apoptosis of PAM cells in the pathogenesis of the SS2 infection.

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“…They can bind to the target mRNA, resulting in translational suppression or degradation of mRNA [13]. Due to the important function of microRNAs, they regulate approximately 30% of the gene transcription involved in a variety of cellular processes, including the immune response to invading pathogens [14]. The miRNAs (i.e., miR-223-3p, miR-150, miR-146b, miR-16, and miR-191), abundantly expressed in T cells, were down-regulated in human immunodeficiency virus (HIV) patients [15].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA expression profiling of peripheral blood mononuclear cells associated with syphilis

Huang

Zhang

et al. 2020

BMC Infect Dis

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Background: Treponema pallidum (T. pallidum) infection evokes significant immune responses, resulting in tissue damage. The immune mechanism underlying T. pallidum infection is still unclear, although microRNAs (miRNAs) have been shown to influence immune cell function and, consequently, the generation of antibody responses during other microbe infections. However, these mechanisms are unknown for T. pallidum. Methods: In this study, we performed a comprehensive analysis of differentially expressed miRNAs in healthy individuals, untreated patients with syphilis, patients in the serofast state, and serologically cured patients. miRNAs were profiled from the peripheral blood of patients obtained at the time of serological diagnosis. Then, both the target sequence analysis of these different miRNAs and pathway analysis were performed to identify important immune and cell signaling pathways. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed for microRNA analysis. Results: A total of 74 differentially regulated miRNAs were identified. Following RT-qPCR confirmation, three miRNAs (hsa-miR-195-5p, hsa-miR-223-3p, hsa-miR-589-3p) showed significant differences in the serofast and serologically cured states (P < 0.05). One miRNA (hsa-miR-195-5p) showed significant differences between untreated patients and healthy individuals. Conclusions: This is the first study of miRNA expression differences in peripheral blood mononuclear cells (PBMCs) in different stages of T. pallium infection. Our study suggests that the combination of three miRNAs has great potential to serve as a non-invasive biomarker of T. pallium infections, which will facilitate better diagnosis and treatment of T. pallium infections.

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MicroRNA mediated regulation of immunity against gram-negative bacteria

Cited by 13 publications

References 179 publications

miR-181a-5p Regulates TNF-α and miR-21a-5p Influences Gualynate-Binding Protein 5 and IL-10 Expression in Macrophages Affecting Host Control of Brucella abortus Infection

miR-181a-5p Regulates TNF-α and miR-21a-5p Influences Gualynate-Binding Protein 5 and IL-10 Expression in Macrophages Affecting Host Control of Brucella abortus Infection

Transcription elements AREB6 and miR-34a affect apoptosis of PAMs by regulating the expression of SS2-related gene PPP1R11

MicroRNA expression profiling of peripheral blood mononuclear cells associated with syphilis

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