Cited by 82Toxoplasma gondii Research StudiesNeuroinflammation and Neurodegeneration MechanismsImmunotoxicology and immune responses

Soluble Factors Released by Toxoplasma gondii-Infected Astrocytes Down-Modulate Nitric Oxide Production by Gamma Interferon-Activated Microglia and Prevent Neuronal Degeneration

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Rozenfeld, Claudia, Martinez, Rodrigo, Figueiredo, Rodrigo T., Bozza, Marcelo T., Lima, Flávia R. S., Pires, Ana Lúcia, Silva, Patrícia M., Bonomo, Adriana +3 more·2003·Infection and Immunity

Abstract

The maintenance of a benign chronic Toxoplasma gondii infection is mainly dependent on the persistent presence of gamma interferon (IFN-γ) in the central nervous system (CNS). However, IFN-γ-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-γ-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-γ-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-γ-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.

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Crossref · 10.1128/iai.71.4.2047-2057.2003

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  • •NO inhibits Toxoplasma infectivity and prevents disease progression to other systems, especially the central nervous system.

    “as well as inhibiting Toxoplasma infectivity and preventing disease progression to other systems, especially the central nervous system CNS [139].”

    From The Role of Reactive Species on Innate Immunity (2022) · cites this paper as [139]

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Authors
Rozenfeld, C., Martinez, R., Figueiredo, R. T., Bozza, M. T., Lima, F. R. S., Pires, A. L., Silva, P. M., Bonomo, A., Lannes-Vieira, J., De Souza, W., & Moura-Neto, V.
Affiliations
  • Instituto de Biofísica Carlos Chagas Filho (BR)
  • Departamento de Anatomia, ICB
  • Universidade Federal do Rio de Janeiro (BR)
  • Instituto Oswaldo Cruz (BR)
  • Departamento de Farmacologia e FarmacodinÂmica, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil
  • Instituto Nacional de Câncer - INCA (BR)
  • Departamento de Imunologia
  • Instituto de Biofísica Carlos Chagas Filho
Venue
Infection and Immunity
Published
2003-04
Volume
71
Issue
4
Pages
2047-2057
ISSN
  • 0019-9567 (ISSN-L)
  • 1098-5522
OpenAlex
W2124890584
Cited by
82
References
76
Citations by year
2026: 1 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 6 · 2014: 5 · 2013: 6 · 2012: 4
FWCI
3.97
Type
journal article
Language
en
Open access
Locations
  • Infection and Immunity (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Arca - Repositório Institucional da Fiocruz (submittedVersion)
Funders
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
  • Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
  • Institut National Du Cancer
Topics
  • Life Sciences › Immunology and Microbiology › Parasitology › Toxoplasma gondii Research Studies
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
Keywords
Toxoplasma gondii, chronic toxoplasmosis, astrocytes, microglia, nitric oxide, interferon-gamma, prostaglandin E2, IL-10, neuroprotection, neurodegeneration, neurite outgrowth, cAMP signaling, protein kinase A, Th1 response, neuroinflammation, conditioned medium
MeSH terms
Cyclic AMP, Animals, Astrocytes, Cells, Cultured, Interferon-gamma, Mice, Inbred BALB C, Neurons, Nitric Oxide, Solubility, Toxoplasma, Dinoprostone, Down-Regulation, Interleukin-10, Culture Media, Conditioned, Microglia, Coculture Techniques, Mice

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