Analysis of Key miRNA/mRNA Functional Axes During Host Dendritic Cell Immune Response to <i>Mycobacterium tuberculosis</i> Based on GEO Datasets

Background Dendritic cells (DCs) play an important role as a bridge between innate and adaptive immunity, and changes in gene expression of DCs during the immune response to Mycobacterium tuberculosis ( M.tb ) may affect the development of tuberculosis. Methods Using systems biology methods, mRNA and miRNA expression profile data of DCs infected with M.tb were obtained. A total of 1398 differentially expressed mRNAs and 79 differentially expressed miRNAs were identified, and a corresponding miRNA-mRNA regulatory network was constructed using Cytoscape 3.9.1 software. The functional annotations and pathway classifications of the miRNA-mRNA network were identified using the DAVID tool. Then, the key pathway modules in the miRNA-mRNA network were screened and subjected to PPI network analysis to identify hub nodes. Subsequently the miRNA/mRNA axis was determined, validated by qRT-PCR, and evaluated through ROC curve analysis. Results The TNF signaling pathway and the Tuberculosis pathway were key pathway modules, with miR-34a-3p/ TNF and miR-190a-3p/ IL1B being the greatest correlations with the two pathway modules. qRT-PCR results showed that IL1B and miR-190a-3p exhibited significant differences in both the H37Ra and BCG infection groups. The AUC of two factors ( IL1B and miR-190a-3p) was 0.9561 and 0.9625, respectively, showing high sensitivity and specificity. Conclusions Consequently, miR-190a-3p/ IL1B might be a good candidate marker to characterize the immune response of DCs to M.tb and a transition signal from innate to adaptive immunity.