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bioRxiv · 10.1101/2021.08.11.456001

Exosomal miR-106b-5p promotes Mtb survival via targeting CREB5 followed by SOAT1-CIDEC and CASP9-CASP3 pathway

chen, h.·li, c.·song, t.·gao, j.·li, w.·yi, z.·fu, y.
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Abstract

Tuberculosis(TB) is one of the top ten fatal diseases, but the research on the mechanism of TB is still not perfect. Exosome, as an important intercellular signal transmission signal vehicle and the mechanism of exosomes in the interaction between macrophages and Mycobacterium tuberculosis(Mtb), is crucial for TB treatment. In the study, we found that exosomes, derived from Mtb-infected macrophage, exhibited differential enrichment in different organs in mice, causing inflammatory cell infiltration in lungs. Further experiments in vitro showed that exosomes resulted in increased lipid synthesis and inhibition of apoptosis in normal macrophages. In order to further explore its molecular mechanism, bioinformatics analysis showed that miR-106b-5p was up-regulated in exosomes. Subsequently, we verified miR-106b-5p was increased through a large number of blood samples from TB patients. In addition, we demonstrated that miR-106b-5p was upregulated in exosomes from Mtb-infected macrophages, which can be engulfed by uninfected macrophages and further result in miR-106b-5p increase. We next found that miR-106b-5p mediated the same effect as the exosomes derived from infected macrophage. Through further research, we indicated that miR-106b-5p promoted lipid droplet accumulation through regulation of Creb5-SOAT1-CIDEC and suppressed macrophage apoptosis via Creb5-CASP9-CASP3 pathway, which ultimately led to Mtb survival. These findings provide a certain theoretical basis and ideas for the diagnosis and treatment of TB as well as the selection of biomarkers.

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chen, h., li, c., song, t., gao, j., li, w., yi, z., fu, y.. 2021-08-11. Exosomal miR-106b-5p promotes Mtb survival via targeting CREB5 followed by SOAT1-CIDEC and CASP9-CASP3 pathway. https://doi.org/10.1101/2021.08.11.456001

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