Related Experiment Video
Updated: Jul 3, 2026
Establishment of Larval Zebrafish as an Animal Model to Investigate Trypanosoma cruzi Motility In Vivo
Published on: September 30, 2017
P2X7 modulatory web in Trypanosoma cruzi infection
C M Cascabulho1, R F S Menna-Barreto, R Coutinho-Silva
1Laboratório de Biologia Celular, Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, FIOCRUZ, Manguinhos, Rio de Janeiro, Brazil 21045-900.
Abstract:
P2X7 is a member of the purinergic receptors family, with extracellular adenosine triphosphate (ATP) as the main agonist, promoting cations influx and membrane permeabilization that can lead to cell death. We previously proposed that extracellular ATP is involved in thymus atrophy induced by Trypanosoma cruzi infection through the induction of CD4+/CD8+ double-positive cell death and that P2X7 could be involved in this process. To further elucidate this possibility raised by in vitro assays, in this study, we used P2X7-/- mice and observed no difference in thymus atrophy or parasitemia when compared to C57Bl/6. We then decided to investigate other aspects of purinergic receptor interplay that could be better evidenced by the infection and observed that (1) thymocytes from infected and noninfected C57Bl/6 mice express P2X4 and P2X7 receptors (Western blotting), but ATP-induced membrane permeabilization only occurs in thymocytes from infected mice; (2) peritoneal macrophages from noninfected C57Bl/6 mice (P2X4+ and P2X7+) are permeabilized by ATP. Although macrophages from infected C57Bl/6 mice are P2X7- but P2X4+, they are resistant to ATP, either through permeabilization or Ca++ influx (fluorimetry); (3) using noninfected P2X7-/- mice, C57Bl/6 infected mice, and different agonistic stimuli, we observed interesting cross-talks among P2X and P2Y receptors (flow cytometry).
Insights
Extracellular ATP and P2X7 receptors do not cause thymus atrophy in Trypanosoma cruzi infections. However, purinergic receptor interactions in thymocytes and macrophages are altered during infection.
Area of Science:
- Immunology
- Cell Biology
- Parasitology
Background:
- P2X7 receptors, activated by extracellular adenosine triphosphate (ATP), mediate cation influx and cell death.
- Extracellular ATP is implicated in thymus atrophy during Trypanosoma cruzi infection, potentially via CD4+/CD8+ T cell death.
- The role of P2X7 in this process warranted further investigation.
Purpose of the Study:
- To investigate the role of P2X7 receptors in Trypanosoma cruzi-induced thymus atrophy.
- To explore the interplay of purinergic receptors (P2X4, P2X7, P2Y) in thymocytes and macrophages during infection.
Main Methods:
- Western blotting to detect P2X4 and P2X7 receptor expression in thymocytes.
- Fluorimetry to assess ATP-induced calcium influx and membrane permeabilization in macrophages.
- Flow cytometry to analyze purinergic receptor cross-talk in thymocytes from infected and P2X7 knockout mice.
Main Results:
- P2X7 knockout mice showed no difference in thymus atrophy or parasitemia compared to wild-type mice.
- Thymocytes from infected mice, but not uninfected, exhibited ATP-induced membrane permeabilization, despite expressing both P2X4 and P2X7.
- Macrophages displayed altered ATP sensitivity and receptor expression profiles upon infection, with evidence of cross-talk between P2X and P2Y receptors.
Conclusions:
- P2X7 receptors are not essential for Trypanosoma cruzi-induced thymus atrophy.
- Infection alters purinergic receptor function in thymocytes and macrophages, suggesting complex regulatory mechanisms.
- Purinergic receptor signaling pathways are dynamically modulated during parasitic infection.
Related Concept Videos
01:22American Trypanosomiasis
01:21Antiprotozoal Agents
01:12GPCR Desensitization
01:30Leishmaniasis