Exosomal miR-181a-5p Protects against MG Infection by Targeting PPM1B and Activating the TLR2-Mediated MyD88/NF-κB Pathway

Abstract BackgroundMycoplasma gallisepticum (MG) is one of the most important pathogens that causes chronic respiratory disease (CRD) in chickens. Exosomes secreted from cells have been well documented to deliver miRNAs to recipient cells to modulate cellular function. The purpose of this current study was to explore the functions of exosomal miR-181a-5p in MG infection and the underlying mechanisms. ResultsHere, we found that miR-181a-5p expression in vivo and in vitro was significantly upregulated after MG infection. Exosomes enriched in MG-infected chicken type-II pneumocytes (CP-II) could selectively load miR-181a-5p and transfer it into recipient DF-1 cells. PPM1B was further identified as the target gene of miR-181a-5p. Overexpression of miR-181a-5p and/or knockdown of PPM1B activated the TLR2-mediated MyD88/NF-κB signaling pathways, whereas inhibition of miR-181a-5p and the overexpression of PPM1B led to the opposite results. In addition, depressing miR-181a-5p significantly reduced the expression of tumor necrosis factors alpha (TNF-α) and interleukin-1β (IL-1β) by MG-induced. Upregulated miR-181a-5p promoted cell proliferation and cell cycle progression and inhibited apoptosis to resist MG infection. Moreover, overexpression of miR-181a-5p significantly depressed pMAG1.2 expression by directly inhibiting PPM1B.ConclusionsTaken together, we conclude that the newly identified primary CP-II cells exosomal miR-181a-5p activates the TLR2-mediated MyD88/NF-κB pathway by directly targeting PPM1B to promote pro-inflammatory cytokines expression for defending against MG infection in recipient DF-1 cells.