Brucella tRNA-derived fragment tRF-Leu-CAG reprograms macrophage polarization for intracellular survival via up-regulation of IL13RA1 expression

The components of OMVs comprise RNA, but the generation as well as the function of OMVs RNA needs to be elucidated. Here, we report that a small non-coding RNA fragment tRF-Leu-CAG, detected in Brucella OMVs, regulates interleukin 13 receptor subunit alpha 1 (IL13RA1) to activate the phosphorylation of Signal Transducer and activator of Transcription 6 (STAT6) via the JAK-STAT6 pathway to reprogram macrophage M2 polarization.

We identified the presence of tRF-Leu-CAG in Brucella OMVs by sRNA sequencing and tRF sequencing from bacterial lysate. tRF-Leu-CAG interacts with argonaute 2 (AGO2) protein to exert its function. Meanwhile, the interleukin 13 receptor subunit alpha 1 (IL13RA1) was proved to be the target genes of tRF-Leu-CAG. Overexpression of phosphorylated STAT6 by western blot further substantiated that tRF-Leu-CAG promotes macrophage M2 polarization via the JAK-STAT6 pathway.