Porphyromonas gingivalis infection alters microRNA composition in extracellular vesicles

Area of Science:

• Oral microbiology and immunology
• Extracellular vesicle research
• MicroRNA biology

Background:

• Periodontitis, often caused by Porphyromonas gingivalis (Pg), involves complex changes in oral cell interactions.
• Extracellular vesicles (EVs) are key mediators of intercellular communication in periodontitis.
• The specific microRNA (miRNA) content of EVs in Pg-infected cells is not fully understood.

Purpose of the Study:

• To identify and characterize miRNAs enriched in EVs derived from Pg-infected cells (Pg-EVs).
• To understand the role of Toll-like receptor (TLR) signaling in miRNA enrichment within Pg-EVs.
• To investigate sequence motifs characteristic of miRNAs concentrated in Pg-EVs.

Main Methods:

• Microarray analysis of miRNA profiles in EVs from Pg-infected THP-1 cells.
• Comparison of miRNA levels in Pg-EVs versus EVs stimulated with lipopolysaccharide (LPS).
• Assessment of TLR signaling inhibition effects on miRNA transcription and investigation of miRNA sequence motifs.

Main Results:

• Eleven miRNAs, including miR-155, were significantly increased in Pg-EVs compared to LPS-stimulated EVs.
• Pg-induced miR-155 upregulation occurred via TLR2, but not TLR4, signaling.
• Enriched miRNAs in Pg-EVs contained specific sequence motifs, such as AGAGGG and GRGGSGC, with high G+C content.

Conclusions:

• Pg infection alters EV miRNA composition independently of TLR4 signaling.
• Specific sequence motifs, particularly those with high G+C content, are associated with miRNA enrichment in Pg-EVs.
• Both innate immune receptor signaling and intrinsic miRNA sequence features likely regulate EV miRNA composition during infection.