MicroRNA-127 Promotes Anti-microbial Host Defense through Restricting A20-Mediated De-ubiquitination of STAT3

• Published in: iScience Vol. 23; no. 1; p. 100763
• Main Authors: Liu, Xiaoyi, Mao, Yun, Kang, Yanhua, He, Long, Zhu, Bo, Zhang, Wei, Lu, Yin, Wu, Qinan, Xu, Dakang, Shi, Liyun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.01.2020; Elsevier
• Subjects: Bacteriology; Immunology; Microbiology; Molecular Mechanism of Behavior; Immunology; Molecular Mechanism of Behavior; Microbiology; Bacteriology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2019.100763

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. [Display omitted] •miR-127 confers the protection against staphylococcal pneumonia•miR-127 augments macrophage anti-microbial responses by regulating STAT3 activity•A20 directly interacts and represses STAT3 K63-ubiquitination•The A20/STAT3 axis mediates the anti-microbial role of miR-127 Molecular Mechanism of Behavior; Immunology; Microbiology; Bacteriology