ArticleJournal of neuroinflammation2017
Priming astrocytes with TNF enhances their susceptibility to Trypanosoma cruzi infection and creates a self-sustaining inflammatory milieu.
Article in Journal of neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 59 citations in OpenAlex.
- Promoting the nuclear retention of HMGB1 attenuates astrocyte senescence.Journal of neuroinflammation · 2026Article
- Beyond cardiac embolism and cryptogenic stroke: unveiling the mechanisms of cerebrovascular events in Chagas disease.Lancet regional health. Americas · 2025Review
- Article
- Bridging the Nervous-Endocrine System and Immune Response, in Human Chagas Disease Pathology.Neuroimmunomodulation · 2025Review
- The beneficial effect of fluoxetine on behavioral and cognitive changes in chronic experimental Chagas disease unveils the role of serotonin fueling astrocyte infection by Trypanosoma cruzi.PLoS neglected tropical diseases · 2024Article
- Hypoxia inducible factor-1α regulates microglial innate immune memory and the pathology of Parkinson's disease.Journal of neuroinflammation · 2024Article
- Article
- Treatment with benznidazole and pentoxifylline regulates microRNA transcriptomic profile in a murine model of Chagas chronic cardiomyopathy.PLoS neglected tropical diseases · 2023Article
- Effects of Acute and Chronic Trypanosoma cruzi Infection on Pregnancy Outcomes in Mice: Parasite Transmission, Mortality, Delayed Growth, and Organ Damage in Pups.The American journal of pathology · 2023Article
- Anxiety, depression, and memory loss in Chagas disease: a puzzle far beyond neuroinflammation to be unpicked and solved.Memorias do Instituto Oswaldo Cruz · 2023Article
- A noncanonical autophagy is involved in the transfer ofAutophagy · 2022Article
- Modulation of miR-145-5p and miR-146b-5p levels is linked to reduced parasite load in H9C2 Trypanosoma cruzi infected cardiomyoblasts.Scientific reports · 2022Article
- Central nervous system commitment in Chagas disease.Frontiers in immunology · 2022Review
- Peripherally misfolded proteins exacerbate ischemic stroke-induced neuroinflammation and brain injury.Journal of neuroinflammation · 2021Article
- Article
- Extracellular Vesicles: Potential Role in Remote Signaling and Inflammation inFrontiers in cell and developmental biology · 2021Review
- Shared neuroimmune and oxidative pathways underpinning Chagas disease and major depressive disorder.Translational psychiatry · 2020Review
- Infectious Diseases and the Lymphoid Extracellular Matrix Remodeling: A Focus on Conduit System.Cells · 2020Review
- Priming Astrocytes With HIV-Induced Reactive Oxygen Species Enhances TheirFrontiers in microbiology · 2020Article
- ExperimentalFrontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn conditions of immunosuppression, the central nervous sty 5ystem (CNS) is the main target tissue for the reactivation of infection by Trypanosoma cruzi, the causative agent of Chagas disease. In experimental T. cruzi infection, interferon gamma (IFNγ)
methodsPrimary astrocyte cultures of neonatal C57BL/6 and C3H/He mice and the human U-87 MG astrocyte lineage were infected with the Colombian T. cruzi strain. Cytokine production, particularly TNF, and TNF receptor 1 (TNFR1/p55) expression were analyzed. Recombinant cytokines (rIFNγ and rTNF), the anti-TNF antibody infliximab, and the TNFR1 modulator pentoxifylline were used to assess the in vitro effects of TNF on astrocyte susceptibility to T. cruzi infection. To investigate the role of TNF on CNS colonization by T. cruzi, infected mice were submitted to anti-TNF therapy.
resultsrTNF priming of mouse and human astrocytes enhanced parasite/astrocyte interaction (i.e., the percentage of astrocytes invaded by trypomastigote parasites and the number of intracellular parasite forms/astrocyte). Furthermore, T. cruzi infection drove astrocytes to a pro-inflammatory profile with TNF and interleukin-6 production, which was amplified by rTNF treatment. Adding rTNF prior to infection fueled parasite growth and trypomastigote egression, in parallel with increased TNFR1 expression. Importantly, pentoxifylline inhibited the TNF-induced increase in astrocyte susceptibility to T. cruzi invasion. In T. cruzi-infected mice, anti-TNF therapy reduced the number of amastigote nests in the brain.
conclusionsOur data implicate TNF as a promoter of T. cruzi invasion of mouse and human astrocytes. Moreover, the TNF-enriched inflammatory milieu and enhanced TNFR1 expression may favor TNF signaling, astrocyte colonization by T. cruzi and egression of trypomastigotes. Therefore, in T. cruzi infection, a self-sustaining TNF-induced inflammatory circuit may perpetuate the parasite cycle in the CNS and ultimately promote cytokine-driven behavioral alterations.
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