Tatiane Figueiredo Morais-Papini1, Jordana Grazziela Alves Coelho-Dos-Reis2, Ana Paula Barbosa Wendling2, Lis Ribeiro do Vale Antonelli3, Pryscilla Fanini Wowk4, Vânia Luiza Deperon Bonato5, Valéria Maria Augusto6, Silvana Elói-Santos7, Olindo Assis Martins-Filho2, Cláudia Martins Carneiro8, Andréa Teixeira-Carvalho9. 1. Grupo Integrado de Pesquisas em Biomarcadores, Centro de Pesquisas René Rachou - FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil; Pós-graduação em Ciências Farmacêuticas (CIPHARMA), Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil. 2. Grupo Integrado de Pesquisas em Biomarcadores, Centro de Pesquisas René Rachou - FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil. 3. Laboratório de Biologia e Imunologia Parasitária, Centro de Pesquisas René Rachou - FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil. 4. Departamento de Bioquímica e Imunologia, Escola de Medicina, Universidade de São Paulo, Ribeirão Preto, Brazil; Instituto Carlos Chagas - FIOCRUZ, Curitiba, Paraná, Brazil. 5. Departamento de Bioquímica e Imunologia, Escola de Medicina, Universidade de São Paulo, Ribeirão Preto, Brazil. 6. Departamento de Propedêutica Complementar, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. 7. Grupo Integrado de Pesquisas em Biomarcadores, Centro de Pesquisas René Rachou - FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil; Departamento de Propedêutica Complementar, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. 8. Pós-graduação em Ciências Farmacêuticas (CIPHARMA), Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil; Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil. 9. Grupo Integrado de Pesquisas em Biomarcadores, Centro de Pesquisas René Rachou - FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil. Electronic address: andreat@cpqrr.fiocruz.br.
Abstract
BACKGROUND: The lung lesions in an individual infected with tuberculosis (TB) are surprisingly variable and independent of each other. However, there is no circulating biomarker yet able to segregate patients according to the extent of lung lesions. MATERIALS AND METHODS: In this study, the phenotypic and functional profile of leukocytes of patients with active pulmonary tuberculosis (TB) and controls (CO) were fully scrutinized by immunophenotyping assays and in vitro short-term whole blood culture. The TB group was subdivided according to the extent of lung lesions as unilateral (UNI) and bilateral (BI). RESULTS: The results show that TB group display an altered leukocyte profile in the peripheral blood with significant lower counts of NK-cells, CD3+CD56+CD16+/- NKT-cells, CD4+T-cells, CD19+B-cells when compared to CO. Increased CD4+T-cells and CD8+T-cell activation was observed by the upregulation of activation markers (HLA-DR) as well as of chemokine receptors (CCR2, CCR3, and CXCR4). In addition, TB group presented a significant decrease proportion of CD14LowCD16+ monocytes despite the increase in HLA-DR expression. Regarding the severity of the disease, in the BI group a reduction in frequency of CD19+CD5+ B-cells and expression of HLA-DR in CD14LowCD16+ monocytes was observed. Furthermore, the extent of lung lesions influences the production of molecules as observed by significantly larger production of IL-4 by neutrophils, total T-cells, CD4+T-cells, CD8+T-cells and CD19+B-cells in UNI as compared to BI. By contrast, in BI group the frequency of high producers of both IL-17+CD4+T-cells and IL-17+CD8+T-cells were significantly increased than UNI, suggesting the deleterious role of these subsets during active pulmonary Mtb infection. CONCLUSION: The immunophenotypic characterization of unilateral and bilateral active TB performed in the present study indicates that the extent of lung lesion could be associated with a fine-tuning between immunological responses during untreated Mtb infection.
BACKGROUND: The lung lesions in an individual infected with tuberculosis (TB) are surprisingly variable and independent of each other. However, there is no circulating biomarker yet able to segregate patients according to the extent of lung lesions. MATERIALS AND METHODS: In this study, the phenotypic and functional profile of leukocytes of patients with active pulmonary tuberculosis (TB) and controls (CO) were fully scrutinized by immunophenotyping assays and in vitro short-term whole blood culture. The TB group was subdivided according to the extent of lung lesions as unilateral (UNI) and bilateral (BI). RESULTS: The results show that TB group display an altered leukocyte profile in the peripheral blood with significant lower counts of NK-cells, CD3+CD56+CD16+/- NKT-cells, CD4+T-cells, CD19+B-cells when compared to CO. Increased CD4+T-cells and CD8+T-cell activation was observed by the upregulation of activation markers (HLA-DR) as well as of chemokine receptors (CCR2, CCR3, and CXCR4). In addition, TB group presented a significant decrease proportion of CD14LowCD16+ monocytes despite the increase in HLA-DR expression. Regarding the severity of the disease, in the BI group a reduction in frequency of CD19+CD5+ B-cells and expression of HLA-DR in CD14LowCD16+ monocytes was observed. Furthermore, the extent of lung lesions influences the production of molecules as observed by significantly larger production of IL-4 by neutrophils, total T-cells, CD4+T-cells, CD8+T-cells and CD19+B-cells in UNI as compared to BI. By contrast, in BI group the frequency of high producers of both IL-17+CD4+T-cells and IL-17+CD8+T-cells were significantly increased than UNI, suggesting the deleterious role of these subsets during active pulmonary Mtb infection. CONCLUSION: The immunophenotypic characterization of unilateral and bilateral active TB performed in the present study indicates that the extent of lung lesion could be associated with a fine-tuning between immunological responses during untreated Mtb infection.