Investigação de vias apoptóticas em células mononucleares humanas induzidas por diferentes cepas vacinais de Mycobacterium bovis BCG

Abstract

Tuberculosis (TB) is the leading cause of death by a single infectious agent, and BCG is the only licensed vaccine for TB with a considerably variable efficacy. This efficacy has been associated with the induction of apoptosis in monocytes/macrophages, and may be the key link between innate and acquired immunity. A few studies suggest better exploring the modulation of molecular pathways of vaccine-induced apoptosis as an important factor to shape the immune response by the BCG vaccine. Thus, the aim of this study was to compare the modulation by Moreau, Danish, Pasteur, and Russia BCG vaccine strains in vitro for 16 and 48 hours, regarding the induction of molecular markers of the apoptosis intrinsic pathway in human mononuclear cells, as well as the cell death profile and cytokine production. The results of mRNA relative quantification showed increased levels (p<0.0001) of NOXA, PUMA, and BCL-XL mainly by the Moreau and Pasteur BCG strains. An MCL-1 higher expression (p=0.0050) was induced by the Danish BCG. As a whole, the expressions of BAD, BAX, and BAK were unaffected. The higher apoptosis levels (p=0.0427) were found for the Moreau BCG strain, compared with the Russia strain. Additionally, significant increases in the levels of IFN-γ (p=0.0078) and TNF (p=0.0429) were observed for the Moreau BCG, compared with baseline and Russia BCG. This study suggests an immunomodulatory profile induced by the Moreau BCG strain, compared with the other BCG vaccine strains.