Role of cytokines and lymphocytes on the efficacy of Posaconazole and Benznidazole in treatment of experimental acute Trypanosoma cruzi infection Alvaro.

Apresentação em tema: "Role of cytokines and lymphocytes on the efficacy of Posaconazole and Benznidazole in treatment of experimental acute Trypanosoma cruzi infection Alvaro."— Transcrição da apresentação:

1 Role of cytokines and lymphocytes on the efficacy of Posaconazole and Benznidazole in treatment of experimental acute Trypanosoma cruzi infection Alvaro José Romanha Centro de Pesquisa René Rachou – FIOCRUZ - MG Rio de Janeiro, July 2009.

2 WT IFN- KO IL-12 KO

3 WT IFN- KO IL-12 KO

4 Mortality, survival and cure of WT, IFN-γ-KO and IL-12-KO mice infected with T.cruzi Y strain and treated with posaconazole and benznidazole Treatment

5 Mortality, survival and cure of WT, IFN-γ-KO and IL-12-KO mice infected with T.cruzi Y strain and treated with posaconazole and benznidazole

6 Mortality, survival and cure of WT, IFN-γ-KO and IL-12-KO mice infected with T.cruzi Y strain and treated with posaconazole and benznidazole

7 Conclusion: Our results demonstrate that either IFN-γ or IL-12 deficiency reduces the efficacy of POS or BZ in the acute murine infection with T.cruzi but also indicate that the anti-T.cruzi activity of POS is much less dependent on the activity of IFN-γ than that of BZ.

8 WT LTCD4+ KO LTCD8+ KO LB KO

9 WT LTCD4+ KO LTCD8+ KO LB KO

10 Survival and cure of WT and CD4 + T-lymphocyte, CD8 + T-lymphocyte, and B-lymphocyte-KO mice infected with the Y strain of T.cruzi and treated with POS or BZ

11 Conclusion: The absence of different lymphocytes activities has distinct effects on the efficacy of POS and BZ in the acute murine infection with T.cruzi, probably reflecting different parasite stages preferentially targeted by the two drugs and distinct cooperation patterns with the host immune system.

12 Collaborators: Marcela L. Ferraz e Rosana O. Alves Laboratório de Parasitologia Celular e Molecular, Centro de Pesquisa René Rachou, FIOCRUZ-MG; Ricardo T. Gazzinelli Laboratório de Imunopatologia, Centro de Pesquisa René Rachou, FIOCRUZ-MG e Departamento de Bioquímica e Imunologia, ICB-UFMG; Julio A. Urbina Laboratório de Química Biológica, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Venezuela