Influência de células T reguladoras na atividade microbicida de pacientes com tuberculose pulmonar e indivíduos saudáveis com teste tuberculínico positivo e negativo frente ao desafio com cepas de Mycobacterium tuberculosis sensíveis e multidroga-resistentes

Abstract

Pre-sensitized/Tb exposed subjects may develop latent TB, which can be reactivated. Here we demonstrate that Purified Protein Derivative (PPD) skin test reactive individuals and TB patients show decreased in vitro microbicidal activity against Mycobacterium tuberculosis hen compare to PPD negative individual (PPD-) using whole blood or CMSP samples. For the present study, we enrolled 13 PPD+, 13 PPD- individuals and 11 TB pulmonary. For microbicidal and infection experiments, we used two clinical susceptible isolates (2220-S1 and 0885-S5), two multidrug-resistant isolates (0530-R3 and 0669-R6) and H37-Rv strain as standard. Comparing increased frequency of regulatory T cells with microbicidal activity; we showed that Tregs could negatively modulate the microbicidal response function, since the Tregs depletion re-established this ability on both PPD+ and TB groups. TGF-β e IL-10 production were elevated among PPD+ individuals, suggesting that it may be related to Tregs cells participation. TB patient showed increased levels of IFN-γ e IL-23 production, suggesting an involvement of Th17 response. Our results suggest that pre-exposure followed by pathogen challenge may increase the chance for the latency/disease development.