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TNF-α blockade impairs in vitro tuberculous granuloma formation and down modulate Th1, Th17 and Treg cytokines

Silva, Djalma A Alves da ; Silva, Marcos V da ; Barros, Cleyson C Oliveira ; Alexandre, Patrícia B Dias ; Timóteo, Rodolfo P ; Catarino, Jonatas S ; Sales-Campos, Helioswilton ; Machado, Juliana R ; Rodrigues, Denise B R ; Oliveira, Carlo J ; Rodrigues, Virmondes Delogu, Giovanni

PloS one, 2018-03, Vol.13 (3), p.e0194430-e0194430 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
TNF-α blockade impairs in vitro tuberculous granuloma formation and down modulate Th1, Th17 and Treg cytokines
Autor: Silva, Djalma A Alves da ; Silva, Marcos V da ; Barros, Cleyson C Oliveira ; Alexandre, Patrícia B Dias ; Timóteo, Rodolfo P ; Catarino, Jonatas S ; Sales-Campos, Helioswilton ; Machado, Juliana R ; Rodrigues, Denise B R ; Oliveira, Carlo J ; Rodrigues, Virmondes
Delogu, Giovanni
Assuntos: Activation ; Antigens ; Arthritis ; Bacillus Calmette-Guerin vaccine ; BCG ; Beads ; Biology and Life Sciences ; Chemokines ; Cytokines ; Disease ; Disease control ; Gene expression ; Granuloma ; Granulomas ; Helper cells ; Immunology ; Infections ; Inflammatory diseases ; Infliximab ; Interleukin 10 ; Interleukin 12 ; Interleukin 17 ; Laboratories ; Leukocytes (mononuclear) ; Lymphocytes T ; Medical treatment ; Medicine and Health Sciences ; Monoclonal antibodies ; Mycobacterium ; Mycobacterium tuberculosis ; Nitric oxide ; Patients ; Peripheral blood mononuclear cells ; Tuberculosis ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α ; γ-Interferon
É parte de: PloS one, 2018-03, Vol.13 (3), p.e0194430-e0194430
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Competing Interests: The authors have declared that no competing interests exist.
Descrição: Tuberculosis (TB) is a granulomatous disease that has affected humanity for thousands of years. The production of cytokines, such as IFN-γ and TNF-α, is fundamental in the formation and maintenance of granulomas and in the control of the disease. Recently, the introduction of TNF-α-blocking monoclonal antibodies, such as Infliximab, has brought improvements in the treatment of patients with chronic inflammatory diseases, but this treatment also increases the risk of reactivation of latent tuberculosis. Our objective was to analyze, in an in vitro model, the influence of Infliximab on the granulomatous reactions and on the production of antigen-specific cytokines (TNF-α, IFN-γ, IL-12p40, IL-10 and IL-17) from beads sensitized with soluble Bacillus Calmette-Guérin (BCG) antigens cultured in the presence of peripheral blood mononuclear cells (PBMC) from TB patients. We evaluated 76 individuals, with tuberculosis active, treated and subjects with positive PPD. Granuloma formation was induced in the presence or absence of Infliximab for up to 10 days. The use of Infliximab in cultures significantly blocked TNF-α production (p <0.05), and led to significant changes in granuloma structure, in vitro, only in the treated TB group. On the other hand, there was a significant reduction in the levels of IFN-γ, IL-12p40, IL-10 and IL-17 after TNF-α blockade in the three experimental groups (p <0.05). Taken together, our results demonstrate that TNF-α blockade by Infliximab directly influenced the structure of granuloma only in the treated TB group, but negatively modulated the production of Th1, Th17 and regulatory T cytokines in the three groups analyzed.
Editor: United States: Public Library of Science
Idioma: Inglês

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TNF-α blockade impairs in vitro tuberculous granuloma formation and down modulate Th1, Th17 and Treg cytokines

Silva, Djalma A Alves da ; Silva, Marcos V da ; Barros, Cleyson C Oliveira ; Alexandre, Patrícia B Dias ; Timóteo, Rodolfo P ; Catarino, Jonatas S ; Sales-Campos, Helioswilton ; Machado, Juliana R ; Rodrigues, Denise B R ; Oliveira, Carlo J ; Rodrigues, Virmondes Delogu, Giovanni

United States: Public Library of Science

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