The PI3K-Akt/mTOR signaling pathway and tuberculosis pathogenesis; the first system biology report

Introduction and Objectives: Tuberculosis (TB) is a major public health problem. It estimated that there are about 10.7 million TB patients throughout the world. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K-Akt-mTOR) signaling pathway has key role in cell growth, differentiation, apoptosis, autophagy, metabolism and infectious disease tuberculosis. Dysregulations of the PI3K-Akt/mTOR signaling pathway seem to have a role in tuberculosis. We performed analysis of the PI3K-Akt/mTOR expression changes in active-TB and latent-TB patients and healthy controls. Materials and Methods: The gene expression profiles of CD4+ T-cells of tuberculosis and healthy individuals was obtained from Gene Expression Omnibus (GEO) database (Accession number: GDS4966; GPL570 platform). Subsequently, the GEO2R analysis was performed for detection of differentially expressed genes (DEGs) in active-TB, LTBI and healthy controls as per Benjamini-Hochberg FDR-adjusted p-values <0.05. Results: Analysis performed revealed that inflammatory cytokines, JAK-STAT signaling, MAPK signaling pathway, autophagy gene expression profiles were distinctly different among TB, LTBI and healthy donors. Foxp3, CTLA-4, TIM1, JAK1, Cox11, BCL11A, TMX3, CXCL10 or PDL2 are overexpressed in active-TB compared to LTBI and healthy controls. Conclusion: Our findings suggest that PI3K-Akt/mTOR signaling pathway is altered during active tuberculosis that may result in altered T regulatory cell function via FOXO1. Previous studies showed that T reg cells are overexpressed in active-TB patients which may result in suppression of Th1 response. Hence, expression of the PI3K-Akt/mTOR signaling pathway could be utilized to determine the activity of tuberculosis infection and monitor its progression and prognosis.

کلیدواژه ها:

Mycobacterium tuberculosis ، the PI3K-Akt/mTOR signaling pathway ، system biology ، pathogenesis.