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

ABSTRACT: Outer membrane vehicles (OMVs) are secreted from gram-negative bacterium to enable bacterial survival and regulate microbial interactions within bacterial communities. 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. Finally, tRF-Leu-CAG and small interfering IL13RA1 facilitates the survival of Brucella in macrophage. Thus, our results highlight the function of tRF-Leu-CAG in Brucella OMVs by reprogramming macrophage M2 polarization to improve the survival of extracellular Brucella. The study unravels a new mechanism of intracellular parasitism and immune escape in Brucella, providing strategy for the mechanisms of other intracellular parasitic bacteria.

ORGANISM(S): Brucella melitensis M5-90

PROVIDER: GSE287747 | GEO | 2025/01/27

REPOSITORIES: GEO