Padrões de expressão gênica em indivíduos com tuberculose ativa e infecção latente, vacinados ou não com o Bacilo de Calmette-Guérin (BCG)

Abstract

INTRODUCTION: Tuberculosis (TB) is a chronic infectious disease difficult to manage due to the different equilibrium states between the infection and the individual’s immune response in its natural evolution. Early identification of active disease is very important for the bacillus dissemination control and prevention of new cases. Several studies attempted to find molecules that may help to distinct stages of disease manifestation, ranging from latent to active disease. In recent years, a global analysis tool that allows the recognition of modulated processes between pathogen and host interaction called systems biology have been employed to assist in the identification of relevant biomarkers in tuberculosis infection course. However, there is a shortage of data in the literature on how the BCG vaccine, widely used against TB worldwide and with a wide spectrum of effects on the organism, can influence the modulation of the immune response and the pathogenesis of the disease. AIM: To characterize the gene expression profile in individuals with active tuberculosis, latent infection and non-infected controls, including the variable of vaccination status with BCG. MATERIAL AND METHODS: To understand the potential biological processes involved in this interaction, we performed bioinformatics analyzes using gene expression data from the public database Gene Expression Omnibus (GEO). Transcriptome data from 3 datasets that evaluated whole blood samples from individuals with active and latent tuberculosis, as well as healthy controls, with their established BCG vaccination status were obtained. RESULTS: Among vaccinated, those with tuberculous disease differ from controls in 4 genes, which are associated with cell death and survival, autophagy, as well as phagossome maturation. When comparing individuals with active TB and latent infection, 3 modulated genes are observed, which are associated with lipid and carbohydrate metabolism, as well as molecular transport. In contrast, among unvaccinated individuals, comparisons between controls individuals, infected and patients presented 100 modulated molecules, with some intersections in modulated pathways between vaccinated individuals. RAB25 and SLC30A3 are upregulated in unvaccinated patients compared to vaccinated. These molecules act on molecular transport, cell movement, cell-cell signaling, as well as carbohydrate metabolism. CONCLUSION: Our results suggest that previous vaccination with BCG interferes in the modulation of specific genes, influencing the pathogenesis of the disease by altering important pathways in infection control. These findings can be applied to the development of new therapies or optimizing existing therapies.