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利什曼原虫感染期间，超级增强子介导的miR146a - 5p转录驱动M2极化。

Super enhancer-mediated transcription of miR146a-5p drives M2 polarization during Leishmania donovani infection.

作者信息

Das Sonali, Mukherjee Sohitri, Ali Nahid

机构信息

Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.

出版信息

PLoS Pathog. 2021 Feb 25;17(2):e1009343. doi: 10.1371/journal.ppat.1009343. eCollection 2021 Feb.

DOI:10.1371/journal.ppat.1009343
PMID:33630975
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7943006/
Abstract

The outcome of Leishmania donovani infection depends upon the dynamic interchanges between M1 and M2 macrophages. Information of the involvement of microRNAs (miRNAs) and epigenetic modifiers in regulating macrophage plasticity during L. donovani infection is still elusive. Differential expression analysis of polarization-regulating miRNAs, revealed significant enrichment of miR146a-5p during Leishmania donovani infection. A sustained enrichment of miR146a-5p was observed in both infected bone marrow derived macrophages (BMDMs) and BALB/c mice organs. We found involvement of miR146a-5p in phagocytosis and survivability of parasites. Moreover, miR146a-5pgot enriched in interleukin 4- stimulated BMDMs, indicating its possible involvement in M2 polarization. Upon transfecting BMDMs with miRVANA anti-146a oligos, M2 markers (CCR7, YM-1, FIZZ-1, arginase-1, IL10 and IL4) and transcription factors (p-STAT6 and c/EBPβ) got depleted with concomitant augmentation of M1-polarizing transcription factors (p-STAT1, AP1 and IRF-1), miR146a target genes (TRAF6 and IRAK1), M1 cytokines (IL12 and TNFα), iNOS, nitric oxide, and nuclear translocation of phospho p-65 subunit. Neutralization of intracellular mature miR146a-5p pool in infected BALB/c mice lower organ parasite burden and expressions of M2 markers and IL10 with enrichment of M1 markers like iNOS and IL12. Additionally, we explored the novel role of super enhancer (SE), a cis-acting regulatory component, to enrich miR146a-5p expression during infection. Enhanced expression and nuclear retention of SE components like BET bromodomain 4 (BRD4) and p300 were found in infected BMDMs. Upon silencing BRD4, expressions of miR146a-5p and M2 markers were down regulated and TRAF6, IRAK1 and iNOS levels increased. STRING V.11 based predication and immune precipitation confirmed the strong interaction amongst BRD4, p300 and RNA pol II (RpbI). Chromatin immune precipitation studies suggested the recruitment of BRD4 at the enhancer loci of miR146a-5p gene during infection. Altogether, our findings revealed a novel role of BRD4/p300-depdendent super-enhancer in regulating miR146a expression during L. donovani infection which in turn mediates M2 polarization and immune-suppression.

摘要

杜氏利什曼原虫感染的结果取决于M1和M2巨噬细胞之间的动态交互作用。关于微小RNA（miRNA）和表观遗传修饰因子在杜氏利什曼原虫感染期间调节巨噬细胞可塑性方面的作用信息仍不清楚。对极化调节性miRNA的差异表达分析显示，在杜氏利什曼原虫感染期间miR146a - 5p显著富集。在感染的骨髓来源巨噬细胞（BMDM）和BALB/c小鼠器官中均观察到miR146a - 5p持续富集。我们发现miR146a - 5p参与了寄生虫的吞噬作用和生存能力。此外，miR146a - 5p在白细胞介素4刺激的BMDM中富集，表明其可能参与M2极化。用miRVANA抗 - 146a寡核苷酸转染BMDM后，M2标志物（CCR7、YM - 1、FIZZ - 1、精氨酸酶 - 1、IL10和IL4）和转录因子（p - STAT6和c/EBPβ）减少，同时M1极化转录因子（p - STAT1、AP1和IRF - 1）、miR146a靶基因（TRAF6和IRAK1）、M1细胞因子（IL12和TNFα）、诱导型一氧化氮合酶（iNOS）、一氧化氮以及磷酸化p - 65亚基的核转位增加。中和感染的BALB/c小鼠细胞内成熟的miR146a - 5p库可降低器官寄生虫负荷以及M2标志物和IL10的表达，同时iNOS和IL12等M1标志物富集。此外，我们探索了超级增强子（SE）这一顺式作用调节元件在感染期间富集miR146a - 5p表达中的新作用。在感染的BMDM中发现SE成分如BET溴结构域4（BRD4）和p300的表达增强和核内滞留。沉默BRD4后，miR146a - 5p和M2标志物的表达下调，TRAF6、IRAK1和iNOS水平升高。基于STRING V.11的预测和免疫沉淀证实了BRD4、p300和RNA聚合酶II（RpbI）之间的强相互作用。染色质免疫沉淀研究表明感染期间BRD4在miR146a - 5p基因的增强子位点募集。总之，我们的研究结果揭示了BRD4/p300依赖性超级增强子在杜氏利什曼原虫感染期间调节miR146a表达中的新作用，这反过来介导了M2极化和免疫抑制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4754/7943006/2fa06ff7c86b/ppat.1009343.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4754/7943006/865537c86f8a/ppat.1009343.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4754/7943006/719097ae93fb/ppat.1009343.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4754/7943006/ac10415d7a05/ppat.1009343.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4754/7943006/23a44672103b/ppat.1009343.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4754/7943006/c7ac16d0303e/ppat.1009343.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4754/7943006/0286878535ce/ppat.1009343.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4754/7943006/2fa06ff7c86b/ppat.1009343.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4754/7943006/865537c86f8a/ppat.1009343.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4754/7943006/719097ae93fb/ppat.1009343.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4754/7943006/ac10415d7a05/ppat.1009343.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4754/7943006/23a44672103b/ppat.1009343.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4754/7943006/c7ac16d0303e/ppat.1009343.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4754/7943006/0286878535ce/ppat.1009343.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4754/7943006/2fa06ff7c86b/ppat.1009343.g007.jpg

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本文引用的文献

[1]
Systems Studies Uncover miR-146a as a Target in Infection Model.

ACS Omega. 2020-5-18

[2]
A chemical inhibitor of heat shock protein 78 (HSP78) from represents a potential antileishmanial drug candidate.

J Biol Chem. 2020-7-17

[3]
Subverts Host Immune Response by Epigenetic Reprogramming of Macrophage M(Lipopolysaccharides + IFN-γ)/M(IL-10) Polarization.

J Immunol. 2020-5-15

[4]
The Role of Notch Signaling in Macrophages during Inflammation and Infection: Implication in Rheumatoid Arthritis?

Cells. 2020-1-2

[5]
Modulation of M2 macrophage polarization by the crosstalk between Stat6 and Trim24.

Nat Commun. 2019-9-25

[6]
The Metabolic Signature of Macrophage Responses.

Front Immunol. 2019-7-3

[7]
Macrophage Polarization: Different Gene Signatures in M1(LPS+) vs. Classically and M2(LPS-) vs. Alternatively Activated Macrophages.

Front Immunol. 2019-5-24

[8]
EB1-3 Chain of IL-35 Along With TGF-β Synergistically Regulate Anti-leishmanial Immunity.

Front Immunol. 2019-4-12

[9]
Toll-Like Receptor and miRNA-let-7e Expression Alter the Inflammatory Response in -Infected Macrophages.

Front Immunol. 2018-11-29

[10]
Relationship of peripheral blood mononuclear cells miRNA expression and parasitic load in canine visceral leishmaniasis.

PLoS One. 2018-12-5

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