| Author | Rozenfeld, Claudia | |
| Author | Martinez, Rodrigo | |
| Author | Figueiredo, Rodrigo T. | |
| Author | Bozza, Marcelo T. | |
| Author | Lima, Flávia R. S. | |
| Author | Pires, Ana Lúcia | |
| Author | Silva, Patrícia M. | |
| Author | Bonomo, Adriana | |
| Author | Lannes-Vieira, Joseli | |
| Author | Souza, Wanderley de | |
| Author | Moura Neto, Vivaldo | |
| Access date | 2020-03-26T20:23:10Z | |
| Available date | 2020-03-26T20:23:10Z | |
| Document date | 2003 | |
| Citation | ROZENFELD, Claudia et al. Soluble Factors Released by Toxoplasma gondii-Infected Astrocytes Down-Modulate Nitric Oxide Production by Gamma Interferon-Activated Microglia and Prevent Neuronal Degeneration. Infection and Immunity, v. 71, n. 4, p. 2047-2057, Apr. 2003. | pt_BR |
| ISSN | 0019-9567 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/40528 | |
| Language | eng | pt_BR |
| Publisher | American Society for Microbiology | pt_BR |
| Rights | restricted access | |
| Subject in Portuguese | Toxoplasma gondii | pt_BR |
| Subject in Portuguese | Microglia | pt_BR |
| Subject in Portuguese | Óxido nítrico | pt_BR |
| Subject in Portuguese | Interferon gama | pt_BR |
| Subject in Portuguese | Fatores solúveis | pt_BR |
| Subject in Portuguese | Degeneração neuronal | pt_BR |
| Title | Soluble factors released by Toxoplasma gondii-infected astrocytes down-modulate nitric oxide production by gamma interferon-activated microglia and prevent neuronal degeneration | pt_BR |
| Type | Article | |
| DOI | 10.1128/iai.71.4.2047-2057.2003 | |
| Abstract | The maintenance of a benign chronic Toxoplasma gondii infection is mainly dependent on the persistent presence of gamma interferon (IFN-gamma) in the central nervous system (CNS). However, IFN-gamma-activated microglia are paradoxically involved in parasitism control and in tissue damage during a broad range of CNS pathologies. In this way, nitric oxide (NO), the main toxic metabolite produced by IFN-gamma-activated microglia, may cause neuronal injury during T. gondii infection. Despite the potential NO toxicity, neurodegeneration is not a common finding during chronic T. gondii infection. In this work, we describe a significant down-modulation of NO production by IFN-gamma-activated microglia in the presence of conditioned medium of T. gondii-infected astrocytes (CMi). The inhibition of NO production was paralleled with recovery of neurite outgrowth when neurons were cocultured with IFN-gamma-activated microglia in the presence of CMi. Moreover, the modulation of NO secretion and the neuroprotective effect were shown to be dependent on prostaglandin E(2) (PGE(2)) production by T. gondii-infected astrocytes and autocrine secretion of interleukin-10 (IL-10) by microglia. These events were partially eliminated when infected astrocytes were treated with aspirin and cocultures were treated with anti-IL-10 neutralizing antibodies and RP-8-Br cyclic AMP (cAMP), a protein kinase A inhibitor. Further, the modulatory effects of CMi were mimicked by the presence of exogenous PGE(2) and by forskolin, an adenylate cyclase activator. Altogether, these data point to a T. gondii-triggered regulatory mechanism involving PGE(2) secretion by astrocytes and cAMP-dependent IL-10 secretion by microglia. This may reduce host tissue inflammation, thus avoiding neuron damage during an established Th1 protective immune response. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Ciências Biológicas. Departamento de Anatomia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Ciências Biológicas. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Ciências Biológicas. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Ciências Biológicas. Departamento de Anatomia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Farmacologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Farmacologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Instituto Nacional de Câncer. Departamento de Medicina Experimental. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Ciências Biológicas. Departamento de Anatomia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Toxoplasma gondii | pt_BR |
| Subject | Soluble Factors | pt_BR |
| Subject | Nitric Oxide | pt_BR |
| Subject | Gamma Interfero | pt_BR |
| Subject | Microglia | pt_BR |
| Subject | Neuronal Degeneration | pt_BR |
| e-ISSN | 1098-5522 | |
| Embargo date | 2022-01-01 | |
