P2X7 Receptor Modulation of the Gut Microbiota and the Inflammasome Determines the Severity of Toxoplasma gondii-Induced Ileitis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animal Study Ethics Statement
2.2. Animals
2.3. Maintenance of T. gondii Cysts
2.4. Experimental Design
2.5. Ileal Parasite Load
2.6. Aminotransferase Assays
2.7. Cytokine Measurements
2.8. Histological Analysis
2.9. Immunohistochemistry (IHC) and Apoptosis Assessment
2.10. Nitric Oxide (NO) Production and Myeloperoxidase Activity Assessment
2.11. Ileal IL-1β Measurement
2.12. RNA Isolation, cDNA Synthesis, and qRT-PCR
2.13. Contractile Activity of Longitudinal Smooth Muscle in the Ileum
2.14. Fecal Microbiota Analysis
2.15. Statistical Analysis
3. Results
3.1. The P2X7 Receptor Is Overexpressed in the Ileum Following T. gondii Infection
3.2. The P2X7 Receptor Protects the Host against T. gondii Infection
3.2.1. Survival Curve
3.2.2. Tissue Damage and Parasite Loading
3.3. P2X7 Modulates Morbidity and the Inflammatory Response in T. gondii Infection
3.3.1. Body Weight and Liver Aminotransferases
3.3.2. Systemic Inflammatory Response
3.3.3. Mucosal Inflammatory Response and Caspase-1 Activation
3.4. Increased Ileal Contractility Is Enhanced in the Absence of the P2X7 Receptor in T. gondii Infection
3.5. Inflammasome-Mediated Immune Response against T. gondii Infection
3.5.1. RT-qPCR
3.5.2. The P2X7 Receptor Modulates NLRP3 and IL-1β Upregulation and NO Downregulation after T. gondii Infection
3.6. The P2X7 Receptor Modulates the Microbiota Associated with T. gondii-Induced Ileitis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Moreira-Souza, A.C.A.; Nanini, H.F.; Rangel, T.P.; da Silva, S.R.B.; Damasceno, B.P.; Ribeiro, B.E.; Cascabulho, C.M.; Thompson, F.; Leal, C.; Santana, P.T.; et al. P2X7 Receptor Modulation of the Gut Microbiota and the Inflammasome Determines the Severity of Toxoplasma gondii-Induced Ileitis. Biomedicines 2023, 11, 555. https://doi.org/10.3390/biomedicines11020555
Moreira-Souza ACA, Nanini HF, Rangel TP, da Silva SRB, Damasceno BP, Ribeiro BE, Cascabulho CM, Thompson F, Leal C, Santana PT, et al. P2X7 Receptor Modulation of the Gut Microbiota and the Inflammasome Determines the Severity of Toxoplasma gondii-Induced Ileitis. Biomedicines. 2023; 11(2):555. https://doi.org/10.3390/biomedicines11020555
Chicago/Turabian StyleMoreira-Souza, Aline Cristina Abreu, Hayandra Ferreira Nanini, Thuany Prado Rangel, Sthefani Rodrigues Batista da Silva, Beatriz Pêgo Damasceno, Beatriz Elias Ribeiro, Cynthia M. Cascabulho, Fabiano Thompson, Camille Leal, Patrícia Teixeira Santana, and et al. 2023. "P2X7 Receptor Modulation of the Gut Microbiota and the Inflammasome Determines the Severity of Toxoplasma gondii-Induced Ileitis" Biomedicines 11, no. 2: 555. https://doi.org/10.3390/biomedicines11020555