ArticlePLoS pathogens2020
PARP1-cGAS-NF-κB pathway of proinflammatory macrophage activation by extracellular vesicles released during Trypanosoma cruzi infection and Chagas disease.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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48 citing papers in PubMed, 66 citations in OpenAlex.
- DNA-PKcs and PARP1 at the interface between DNA damage responses and cGAS-STING signaling: context-dependent roles and therapeutic implications.Cancer biology & therapy · 2026Review
- Hypercoagulability and vascular proinflammatory activation promote cardiac-cerebral fibrinogenesis in a rodent model of Chagas disease.Emerging microbes & infections · 2026Article
- Hijacking Host Communication: The Central Role of Extracellular Vesicles in Infectious Disease Pathogenesis.Cells · 2026Review
- Emerging roles of the cGAS/STING pathway in cardiovascular diseases.The Journal of clinical investigation · 2026Review
- Bugs as drugs: parasite biomolecules as novel therapeutics against breast cancer.American journal of physiology. Cell physiology · 2026Review
- The Role of Immunogenetics in the Host-Parasite Interaction of Chagas Disease: Implications for Personalized Medicine.Tropical medicine and infectious disease · 2025Review
- PARP1-NFATc1-PD1 pathway of maturation and stability of CD8iScience · 2025Article
- Oxidative Stress in HIV-Associated Neurodegeneration: Mechanisms of Pathogenesis and Therapeutic Targets.International journal of molecular sciences · 2025Review
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- Towards a map of the immune system manipulation network byFrontiers in cellular and infection microbiology · 2025Review
- cGAS-STING signaling in cardiovascular diseases.Frontiers in immunology · 2024Review
- Protective Effects of Baicalein on Lipopolysaccharide-Induced AR42J PACs through Attenuation of Both Inflammation and Pyroptosis via Downregulation of miR-224-5p/PARP1.Mediators of inflammation · 2024Article
- Overview of extracellular vesicles in pathogens with special focus on human extracellular protozoan parasites.Memorias do Instituto Oswaldo Cruz · 2024Review
- The effect of Banxia-houpo decoction on CUMS-induced depression by promoting M2 microglia polarization via TrkA/Akt signalling.Journal of cellular and molecular medicine · 2023Article
- cGAS-STING Pathway Activation during Trypanosoma cruzi Infection Leads to Tissue-Dependent Parasite Control.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- PARPs and ADP-Ribosylation in Chronic Inflammation: A Focus on Macrophages.Pathogens (Basel, Switzerland) · 2023Review
- Acute muscle mass loss was alleviated with HMGB1 neutralizing antibody treatment in severe burned rats.Scientific reports · 2023Article
- Borrelia burgdorferi Engages Mammalian Type I IFN Responses via the cGAS-STING Pathway.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- A noncanonical response to replication stress protects genome stability through ROS production, in an adaptive manner.Cell death and differentiation · 2023Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Trypanosoma cruzi (T. cruzi) is the etiological agent of Chagas cardiomyopathy. In the present study, we investigated the role of extracellular vesicles (Ev) in shaping the macrophage (Mφ) response in progressive Chagas disease (CD). We purified T. cruzi Ev (TcEv) from axenic parasite cultures, and T. cruzi-induced Ev (TEv) from the supernatants of infected cells and plasma of acutely and chronically infected wild-type and Parp1-/- mice. Cultured (Raw 264.7) and bone-marrow Mφ responded to TcEV and TEv with a profound increase in the expression and release of TNF-α, IL-6, and IL-1β cytokines. TEv produced by both immune (Mφ) and non-immune (muscle) cells were proinflammatory. Chemical inhibition or genetic deletion of PARP1 (a DNA repair enzyme) significantly depressed the TEv-induced transcriptional and translational activation of proinflammatory Mφ response. Oxidized DNA encapsulated by TEv was necessary for PARP1-dependent proinflammatory Mφ response. Inhibition studies suggested that DNA-sensing innate immune receptors (cGAS>>TLR9) synergized with PARP1 in signaling the NFκB activation, and inhibition of PARP1 and cGAS resulted in >80% inhibition of TEv-induced NFκB activity. Histochemical studies showed intense inflammatory infiltrate associated with profound increase in CD11b+CD68+TNF-α+ Mφ in the myocardium of CD wild-type mice. In comparison, chronically infected Parp1-/- mice exhibited low-to-moderate tissue inflammation, >80% decline in myocardial infiltration of TNF-α+ Mφ, and no change in immunoregulatory IL-10+ Mφ. We conclude that oxidized DNA released with TEv signal the PARP1-cGAS-NF-κB pathway of proinflammatory Mφ activation and worsens the chronic inflammatory pathology in CD. Small molecule antagonists of PARP1-cGAS signaling pathway would potentially be useful in reprogramming the Mφ activation and controlling the chronic inflammation in CD.
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