ArticleInfection and immunity2003
Soluble factors released by Toxoplasma gondii-infected astrocytes down-modulate nitric oxide production by gamma interferon-activated microglia and prevent neuronal degeneration.
Article in Infection and immunity, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 81 citations in OpenAlex.
- Latent Cerebral Toxoplasma Gondii Infection Induces the Kynurenine Pathway and Production of Neurotoxic Metabolites.International journal of tryptophan research : IJTR · 2026Article
- Pathological mechanisms of glial cell activation and neurodegenerative and neuropsychiatric disorders caused byFrontiers in microbiology · 2024Review
- The Role of Reactive Species on Innate Immunity.Vaccines · 2022Review
- Epidemiology, Pathophysiology, Diagnosis, and Management of Cerebral Toxoplasmosis.Clinical microbiology reviews · 2021Review
- Head-to-head comparisons of Toxoplasma gondii and its near relative Hammondia hammondi reveal dramatic differences in the host response and effectors with species-specific functions.PLoS pathogens · 2020Article
- Characteristics of Infection Immunity Regulated byFrontiers in immunology · 2018Article
- Priming astrocytes with TNF enhances their susceptibility to Trypanosoma cruzi infection and creates a self-sustaining inflammatory milieu.Journal of neuroinflammation · 2017Article
- Chronic Toxoplasma gondii infection enhances β-amyloid phagocytosis and clearance by recruited monocytes.Acta neuropathologica communications · 2016Article
- Role of the chemokine receptor CCR5-dependent host defense system in Neospora caninum infections.Parasites & vectors · 2015Article
- Article
- Dual transcriptional profiling of mice and Toxoplasma gondii during acute and chronic infection.BMC genomics · 2014Article
- Role of IFN-γ and LPS on neuron/glial co-cultures infected by Neospora caninum.Frontiers in cellular neuroscience · 2014Article
- Transcriptome analysis of mouse brain infected with Toxoplasma gondii.Infection and immunity · 2013Article
- Brain inflammation and microglia: facts and misconceptions.Experimental neurobiology · 2013Article
- Toxoplasmosis.Handbook of clinical neurology · 2013Article
- Article
- Prophylactic and therapeutic targeting of the neurokinin-1 receptor limits neuroinflammation in a murine model of pneumococcal meningitis.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- Microglia in infectious diseases of the central nervous system.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2009Review
- Malondialdehyde, glutathione, and nitric oxide levels in Toxoplasma gondii seropositive patients.The Korean journal of parasitology · 2008Article
- Neurogenic exacerbation of microglial and astrocyte responses to Neisseria meningitidis and Borrelia burgdorferi.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.