Análisis molecular y funcional de la respuesta de macrófagos de pacientes con diabetes a la infección in vitro por Mycobacterium tuberculosis

Abstract

The molecular mechanisms that lead to tuberculosis-diabetes comorbidity are only partially known. In this work, a transcriptomic study focused on tuberculosis-diabetes disease associated with poor glycaemic control was carried out in patients with type 2 diabetes (DM2), as these subjects are at high risk of becoming ill with tuberculosis. Human blood samples from five groups of individuals: healthy controls (CTRL), tuberculosis (TB), TB-Type 2 diabetes comorbidity (TB-DM2), DM2 patients (HbA1c < 8.9%) and DM2 patients with poor glycaemic control (PDM2; HbA1c > 10%) were analyzed using differential expression microarrays. The differentially expressed genes (DEG) specific for TB-DM2 and PDM2 (P < 0.05, fold change > 2) were analyzed throughout a network strategy for the identification of potential molecular patterns linking PDM2 and TB-DM2. OSM, PRKCD and SOCS3 were found as potential key regulatory genes of immune pathways that drives the susceptibility of PDM2 patients to develop TB. RT-qPCR assays confirmed the induction of the OSM, PRKCD and SOCS3 genes in patients with TB-DM2. Furthermore, these molecules showed a protein-protein interaction network scored composed of 19 proteins and 30 pathways interactions. These analyzes suggest that poorly controlled DM2 leads to a transcriptional change that modifies the expression of key regulatory molecules associated with the poor immune response observed in patients with TB and provides essential information to better understand the molecular pathology of TB-DM2.