Envolvimento da vitamina D na resposta inflamatória durante infecção experimental por Mycobacterium bovis BCG: análise da formação de corpúsculos lipídicos e síntese de mediadores inflamatórios

Abstract

Tuberculosis is the leading cause of death from a single infectious agent in the world, responsible for 10M new cases annually. It is a disease caused by mycobacteria from the Mycobacterium tuberculosis complex, characterized by the infection of innate immune cells in the lung. Macrophages are the main cells involved in resolution of infection, through cell recruitment and synthesis of cytokines, reactive oxygen and nitrogen species, antimicrobial peptides and lipid mediators, such as prostaglandin E2. The pathogen is able to subvert the cell’s machinery to its advantage, leading to inhibition of antimicrobial responses and favoring an adipogenic and anti-inflammatory environment that allows its survival within the cell. TB treatment is done with a 4 antibiotic regimen, but due to inadequate or discontinued treatment, drugresistent lineages have risen. In the pre-antibiotic era, vitamin D was used to treat TB. Studies have shown that it was able to potentiate antimicrobial peptide production. Thus, the aim of this work is to evaluate the effect of vitamin D on lipid body formation and lipid mediator synthesis during experimental M. bovis BCG infection in vivo and in vitro. For that, C57/BL6 mice were intrapleurally injected with BCG and treated or not with 2.5IU vitamin D. Also, murine macrophages were infected in vitro, treated or no with 1, 10 or 100nM of vitamin D. Our results demonstrate that vitamin D is inhibits neutrophil migration in infected mice, as well as lipid body formation and PGE2 synthesis, both in vivo and in vitro. Also, vitamin D was able to partially inhibit PPAR-γ expression in infected macrophages and potentiated TNF-α production. These data suggest a protective role for vitamin D during M. bovis BCG infection, as it seems to potentiate a pro-inflammatory response.