Author | Souza, Victor Barreto de | |
Author | Pacheco, Graziela J. | |
Author | Silva, Adriana R. | |
Author | Faria Neto, Hugo C. Castro | |
Author | Bozza, Patrícia T. | |
Author | Saraiva, Elvira M. | |
Author | Bou-Habib, Dumith Chequer | |
Access date | 2019-12-31T18:44:08Z | |
Available date | 2019-12-31T18:44:08Z | |
Document date | 2006 | |
Citation | SOUZA, Victor Barreto de et al. Increased Leishmania Replication in HIV-1–Infected Macrophages Is Mediated by Tat Protein through Cyclooxygenase-2 Expression and Prostaglandin E2 Synthesis. Journal of Infectious Diseases, v. 196, p. 846-854, Sept. 2006. | pt_BR |
ISSN | 0022-1899 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/38913 | |
Language | eng | pt_BR |
Publisher | Oxford University Press | pt_BR |
Rights | restricted access | pt_BR |
Subject in Portuguese | Leishmania | pt_BR |
Subject in Portuguese | Macrófagos infectados pelo HIV-1 | pt_BR |
Subject in Portuguese | Síntese de prostaglandina E2 | pt_BR |
Subject in Portuguese | HIV-1 | pt_BR |
Title | Increased Leishmania replication in HIV-1-infected macrophages is mediated by tat protein through cyclooxygenase-2 expression and prostaglandin E2 synthesis | pt_BR |
Type | Article | pt_BR |
DOI | 10.1086/506618 | |
Abstract | Protozoan parasites of the genus Leishmania frequently occur as opportunistic pathogens in human immunodeficiency virus type 1 (HIV-1)-infected individuals, but the mechanisms underlying protozoan growth in this context are poorly understood. Here, we demonstrate that the HIV-1 Tat protein drives Leishmania replication in primary human macrophages. We found that Leishmania growth doubled in HIV-1-infected macrophages and that anti-Tat antibodies reduced the exacerbated protozoan replication by 70%. Recombinant Tat increased Leishmania replication and overrode the leishmanicidal effect induced by interferon-gamma , allowing Leishmania replication even in the presence of this cytokine. Tat induced cyclooxygenase (COX)-2 expression and prostaglandin E2 (PGE2) synthesis, and a COX-2 inhibitor abolished the Tat-mediated augmentation of Leishmania replication. Moreover, PGE2 increased Leishmania growth, which was abrogated by anti-transforming growth factor (TGF)- beta1 monoclonal antibodies. Neutralization of TGF-beta1 reduced parasite growth in Leishmania-infected macrophages exposed to Tat by 50%. Our findings suggest that Tat generates a milieu permissive to Leishmania growth in individuals infected with HIV-1. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Prof. Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Fisiologia e Farmacodinâmica. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Fisiologia e Farmacodinâmica. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Fisiologia e Farmacodinâmica. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Prof. Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Laboratório de Imunologia Clínica. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | Leishmania | pt_BR |
Subject | HIV-1–Infected Macrophages | pt_BR |
Subject | Cyclooxygenase-2 | pt_BR |
Subject | Prostaglandin E2 Synthesis | pt_BR |
e-ISSN | 1537-6613 | |
Embargo date | 2025-01-01 | |