Author | Pinheiro, R. O. | |
Author | Oliveira, E. B. de | |
Author | Santos, G. dos | |
Author | Silva, G. M. Sperandio da | |
Author | Silva, B. J. de Andrade | |
Author | Teles, R. M. B. | |
Author | Milagres, A. | |
Author | Sarno, E. N. | |
Author | Dalcolmo, M. P. | |
Author | Sampaio, E. P. | |
Access date | 2015-09-21T17:25:43Z | |
Available date | 2015-09-21T17:25:43Z | |
Document date | 2013 | pt_BR |
Citation | PINHEIRO, R. O. et al. Different immunosuppressive mechanisms in multi-drug-resistant tuberculosis and non-tuberculous mycobacteria patients. Clinical and Experimental Immunology, v. 171, p. 210-219, 2013. | pt_BR |
ISSN | 1365-2249 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/11768 | |
Language | por | pt_BR |
Publisher | British Society for Immunology | pt_BR |
Rights | open access | pt_BR |
Title | Different immunosuppressive mechanisms in multi-drug-resistant tuberculosis and non-tuberculous mycobacteria patients | pt_BR |
Type | Article | pt_BR |
DOI | 10.1111/cei.12007 | pt_BR |
Abstract | Previous studies have demonstrated that cells from both multi-drugresistant
tuberculosis (MDR-TB) and non-tuberculous mycobacteria (NTM)
patients respond poorly to mycobacterial antigens in vitro. In the present
study, we compared the in vitro response of cells isolated from sensitive TB
(NR-TB)-, MDR-TB- and NTM-infected patients. Analysis of T cell phenotype
ex vivo revealed that both MDR-TB and NTM patients present an
increased percentage of CD4+CD25+- forkhead box protein 3 (FoxP3)+ and
CD4+CD25+CD127- regulatory T (Treg) cells when compared to NR-TB.
Increased numbers of Treg cells and interleukin (IL)-10 serum levels
were detected in MDR-TB, whereas elevated serum transforming growth
factor (TGF)-b was found in the NTM group. Cells of MDR-TB patients
stimulated with early secretory antigenic target (ESAT)-6, but not purified
protein derivative (PPD), showed a lower frequency of CD4+/interferon
(IFN)-g+ T cells and enhanced CD4+CD25+FoxP3+, CD4+CD25+CD127- and
CD4+CD25+IL-10+ T cell population. In addition, increased IL-10 secretion
was observed in cultured MDR-TB cells following ESAT-6 stimulation, but
not in NR-TB or NTM patients. In vitro blockade of IL-10 or IL-10Ra
decreased the CD4+CD25+FoxP3+ frequencies induced by ESAT-6 in MDRTB,
suggesting a role of IL-10 on impaired IFN-g responses seen in MDR-TB.
Depletion of CD4+CD25+ T lymphocytes restored the capacity of MDR-TB
T cells to respond to ESAT-6 in vitro, which suggests a potential role for
Treg/T regulatory 1 cells in the pathogenesis of MDR-TB. Together, our
results indicate that although the similarities in chronicity, NTM- and MDRTB-
impaired antigenic responses involve different mechanisms. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sérgio Arouca. Centro de Referência Professor Hélio Fraga. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Doença de Chagas. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Hospital Municipal Raphael de Paula Souza. Unidade de Saúde. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sérgio Arouca. Centro de Referência Hélio Fraga. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil / National Institutes of Health, NIH. Laboratory of Clinical Infectious Diseases, LCID/NIAID. Immunopathogenesis Section. Bethesda, WA, USA. | pt_BR |
Subject | IL-10 | pt_BR |
Subject | Immunosuppression | pt_BR |
Subject | MDR-TB | pt_BR |
Subject | NTM | pt_BR |
Subject | Regulatory T cells | pt_BR |
DeCS | Imunossupressão | pt_BR |
DeCS | Interleucina-10 | pt_BR |