Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/40528
Title: Soluble factors released by Toxoplasma gondii-infected astrocytes down-modulate nitric oxide production by gamma interferon-activated microglia and prevent neuronal degeneration
Authors: Rozenfeld, Claudia
Martinez, Rodrigo
Figueiredo, Rodrigo T.
Bozza, Marcelo T.
Lima, Flávia R. S.
Pires, Ana Lúcia
Silva, Patrícia M.
Bonomo, Adriana
Lannes-Vieira, Joseli
Souza, Wanderley de
Moura Neto, Vivaldo
Affilliation: Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Ciências Biológicas. Departamento de Anatomia. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Ciências Biológicas. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Ciências Biológicas. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Ciências Biológicas. Departamento de Anatomia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Farmacologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Farmacologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Câncer. Departamento de Medicina Experimental. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Ciências Biológicas. Departamento de Anatomia. Rio de Janeiro, RJ, Brasil.
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.
Keywords: Toxoplasma gondii
Soluble Factors
Nitric Oxide
Gamma Interfero
Microglia
Neuronal Degeneration
keywords: Toxoplasma gondii
Microglia
Óxido nítrico
Interferon gama
Fatores solúveis
Degeneração neuronal
Issue Date: 2003
Publisher: American Society for Microbiology
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.
DOI: 10.1128/iai.71.4.2047-2057.2003
ISSN: 0019-9567
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

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