Avaliação dos diferentes parâmetros da resposta imune de indivíduos com teste tuberculínico positivo ou negativo perante isolados clínicos de M. tuberculosis sensíveis e multidroga resistentes

Abstract

Immunity against tuberculosis depends on the establishment of an effective Th1 response, with IFN- production, a pivotal cytokine to the activation of macrophages and bacilli destruction. It is known that several factors are related to the host s resistance to tuberculosis. In the present work, the influence of T regulatory cells (Tregs) in the immune response against Mtb was evaluated in whole blood and PBMC cultures from tuberculin skin test positive (TST+) and tuberculin skin test negative (TST-) individuals. Paralelly, we also evaluated if different levels of resistance to anti-mycobacterial drugs displayed by different Mtb clinical isolates could interfere with the cytokine profile, Tregs frequency, and with its proliferative capacity on both PBMC and whole blood cultures from TST+ and TST- subjects. Twenty-two healthy volunteers were invited to participate in our study, 11 TST+ and 11 TST-. Twelve Mtb clinical isolates were used, 6 drug-resistant and 6 drug-susceptible. Our data shows that differences in drug susceptibility did not affected any of the evaluated parameters. In the other hand, TST status correlated with differences in Treg frequencies, which was significantly elevated among TST+ when compared to TSTsubjects. The increase in Tregs was also associated with a decrease in the microbicidal effect observed in whole blood cultures from TST+, when compared to TST-. This association was confirmed through the depletion of Tregs, which restored the microbicidal activity and an increase in IFN-, IL-2, IL10, and TNF- when compared to undepleted cultures. Data presented here supports the hypothesis that pre-exposure to MTB, represented by a positive TST result, may increase the number of Treg cells, which in turn could affect negatively the establishment of a protective immunity against TB in TST+ individuals