Possible microRNA-mediated alterations of gene expression in lipoteichoic acid-stimulated neutrophils

Abstract

Introduction: Lipoteichoic acid (LTA) is a major cell wall component of Gram-positive bacteria. As an agonist of toll-like receptor-2, LTA might stimulate immune cells and contribute to the pathogenesis of sepsis. This study aimed to explore the possible miRNA-mediated gene expression alterations in neutrophils stimulated with LPA.

Methods: The neutrophils isolated from peripheral blood of a healthy donor were treated with either Staphylococcus aureus LTA or water for 16 hours, and the miRNA and mRNA expression profiles were assessed and analyzed with next-generation sequencing and bioinformatics approaches.

Results: A total of 38 differentially expressed miRNAs and 342 differentially expressed genes were identified between LTA-treated and vehicle-treated neutrophils. Using gene ontology analysis of the differentially expressed genes, the significantly enriched biological processes, such as defense response and positive regulation of cell migration, and significantly enriched pathways, such as cytokine-cytokine receptor interaction, were identified. Gene ontology analysis of differentially expressed miRNAs found the significantly enriched biological processes included signal transduction and cell communication. Using miRNA target-predicting tools, we found 4 microRNAs, including hsa-miR-34a-5p, hsa-miR-34c-5p, hsa-miR-708-5p, and hsa-miR-1271-5p, and five target genes, including CACNB3, HBEGF, MET, TNS3, and TTYH3, might play important roles in LTA-induced changes in neutrophils.

Conclusions: We identified some changes of miRNAs and mRNAs in neutrophils treated with LTA. Further studies are needed to understand detailed mechanisms.