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Published on: June 15, 2016
MicroRNA-127 Promotes Anti-microbial Host Defense through Restricting A20-Mediated De-ubiquitination of STAT3
Xiaoyi Liu1, Yun Mao2, Yanhua Kang3
1Department of Immunology and Medical Microbiology, Nanjing University of Chinese Medicine, Nanjing, China.
Abstract:
The increasing rising of multiple drug-resistant Staphylococcus aureus has become a major public health concern, underscoring a pressing need for developing therapies essentially based on the understanding of host defensive mechanism. In the present study, we showed that microRNA (miR)-127 played a key role in controlling bacterial infection and conferred a profound protection against staphylococcal pneumonia. The protective effect of miR-127 was largely dependent on its regulation of macrophage bactericidal activity and the generation of IL-22, IL-17, and anti-microbial peptides (AMPs), the pathway primarily driven by STAT3. Importantly, we revealed that the ubiquitin-editing enzyme A20, a genuine target of miR-127, specifically interacted with and repressed K63-ubiquitination of STAT3, thereby compromising its phosphorylation upon bacterial infection. Thus, our data not only identify miR-127 as a non-coding molecule with anti-bacterial activity but also delineate an unappreciated mechanism whereby A20 regulates STAT3-driven anti-microbial signaling via modulating its ubiquitination.
Insights
MicroRNA-127 protects against Staphylococcus aureus pneumonia by boosting macrophage defenses. It targets A20, a protein that regulates STAT3 signaling crucial for controlling bacterial infections.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- Multiple drug-resistant Staphylococcus aureus poses a significant public health threat.
- Developing new therapies requires understanding host defense mechanisms against bacterial infections.
Purpose of the Study:
- To investigate the role of microRNA (miR)-127 in host defense against Staphylococcus aureus.
- To elucidate the molecular mechanism by which miR-127 confers protection.
Main Methods:
- Assessing the protective effect of miR-127 in a staphylococcal pneumonia model.
- Analyzing the regulation of macrophage bactericidal activity and cytokine production (IL-22, IL-17).
- Investigating the interaction between miR-127, A20, and STAT3 ubiquitination and phosphorylation.
Main Results:
- miR-127 significantly protects against staphylococcal pneumonia.
- miR-127 enhances macrophage bactericidal activity and promotes IL-22, IL-17, and antimicrobial peptide generation via STAT3.
- A20, a target of miR-127, inhibits STAT3 phosphorylation by repressing its K63-ubiquitination.
Conclusions:
- miR-127 acts as a non-coding molecule with potent anti-bacterial activity.
- A20 regulates STAT3-driven antimicrobial signaling by modulating STAT3 ubiquitination, revealing a novel host defense pathway.
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