MicroRNA-125a Inhibits Autophagy Activation and Antimicrobial Responses during Mycobacterial Infection
| Autor: | Jin Kyung Kim, Eun-Kyeong Jo, Soo Yeon Kim, Jae-Min Yuk, Tae Sung Kim, Chul-Su Yang, Hyo Sun Jin |
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| Rok vydání: | 2015 |
| Předmět: |
Immunology
UVRAG AMP-Activated Protein Kinases Biology Cell Line Mycobacterium tuberculosis Mice Immune system RNA interference Autophagy Animals Immunology and Allergy Gene silencing Macrophage RNA Small Interfering Tuberculosis Pulmonary Mice Knockout Regulation of gene expression Macrophages Tumor Suppressor Proteins biology.organism_classification Toll-Like Receptor 2 Cell biology Mice Inbred C57BL MicroRNAs Gene Expression Regulation Myeloid Differentiation Factor 88 RNA Interference Signal Transduction |
| Zdroj: | The Journal of Immunology. 194:5355-5365 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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