Evaluation of the overall IFN-gamma and IL-17 pro-inflammatory responses after DNA therapy of tuberculosis

Author(s):Show less -

Zarate-Blades, Carlos R. ^[1] ; Rodrigues, Rodrigo F. ^[1] ; Souza, Patricia R. M. ^[1] ; Rios, Wendy M. ^[1] ; Soares, Luana S. ^[1] ; Rosada, Rogerio S. ^[1] ; Brandao, Izaira T. ^[1] ; Masson, Ana Paula ^[1] ; Floriano, Elaine M. ^[2] ; Ramos, Simone G. ^[2] ; Silva, Celio L. ^[1]

Affiliation

^[1] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Biochem & Immunol, Ctr TB Res, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Pathol, Sao Paulo - Brazil

• Document type: Journal article
• Source: HUMAN VACCINES & IMMUNOTHERAPEUTICS; v. 9, n. 5, p. 1093-1103, MAY 1 2013.
• Web of Science Citations: 9

Abstract

Despite the enormous efforts displayed globally in the fight against tuberculosis, the disease incidence has modified slightly, which has led to a renewed interest in immunotherapy. In general, successful immunotherapeutic candidates against tuberculosis are agents that can trigger strong, specific pro-inflammatory responses, especially of the T-helper (Th) 1 pattern. However, how these pro-inflammatory agents effectively kill the bacteria without eliciting immunopathology is not well understood. We reasoned that, in addition to the specific immune response elicited by immunotherapy, the evaluation of the overall pro-inflammatory responses should provide additional and valuable information that will be useful in avoiding immunopathology. We evaluated the overall IFN- and IL-17 pro-inflammatory responses among CD4(+), CD8(+) and T cells in the lungs of mice that were infected with M. tuberculosis and treated with a DNA vaccine in an immunotherapeutic regimen. Our results demonstrate that mice that effectively combat the pathogen develop a strong, specific Th1 immune response against the therapeutic antigen and have reduced lung inflammation, present in parallel a fine-tuning in the total IFN-- and IL-17-mediated immunity in the lungs. This modulation of the total immune response involves reducing the Th17 cell population, augmenting CD8(+) T cells that produce IFN- and increasing the total T cell frequency. These results stress the importance of a broad evaluation of not only the specific immune response at the time to evaluate new immune interventional strategies against tuberculosis but also non-conventional T cells, such as T lymphocytes. (AU)

• FAPESP's process: 06/05963-8 - Evaluation of gamma-delta T cells as effector lymphocytes and antigen-presenting cells in prophylaxis and immunotherapy against tuberculosis with DNA vaccines
• Grantee: Carlos Rodrigo Zarate Blades
• Support Opportunities: Scholarships in Brazil - Post-Doctoral