The Giardial Arginine Deiminase Participates in Giardia-Host Immunomodulation in a Structure-Dependent Fashion via Toll-like Receptors
Abstract
:1. Introduction
2. Results
2.1. GlADI Exerts Immunomodulation by Activating TLRs
2.2. GlADI Interacts with the Host Immune System through TLR2 and TLR4
2.3. The Forces Maintaining the 3D Structure of GlADI Could Be a Pivotal Factor in Activating TLRs
2.4. Predicted Interactions between the AlphaFold-Predicted Structure of GlADI and TLR2-TLR1
2.5. Predicted Interactions between the AlphaFold-Predicted Structure of GlADI and TLR4-MD-2
2.6. GlADI Induces Cytokine Production of DCs
3. Discussion
4. Materials and Methods
4.1. Recombinant GlADI Expression and Endotoxin Removal
4.2. Reporter Cell Lines
4.3. GlADI-TLRs Interaction Assays
4.4. Dendritic Cells Culturing and Stimulation with GlADI
4.5. Quantitation of Dendritic Cells Cytokines Production
4.6. Protein Thermal Shift Assay
4.7. Fluorescence Emission Spectra
4.8. Prediction of the Three-Dimensional (3D) Structure of GlADI
4.9. Prediction of the Probably Binding Mode of GlADI to TLRs by Using the AlphaFold-Predicted Structure and Molecular Docking
4.10. Statistical Analyses
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Melting Temperatures of GlADI (°C) | ||||||||
---|---|---|---|---|---|---|---|---|
[NaCl] mM | pH 5.0 | pH 6.0 | pH 6.5 | pH 7.0 | pH 7.5 | pH 8.0 | pH 9.0 | pH 9.5 |
0 | 55.98 | 59.14 | 55.88 | 55.64 | 60.34 | 58.96 | 50.04 | 56.99 |
200 | 49.82 | 60.94 | 60.97 | 63.01 | 70.56 | 56.4 | 59.74 | 56.24 |
400 | 57.04 | 50.59 | 47.17 | 48.12 | 53.57 | 52.05 | 51.93 | 56.84 |
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Fernández-Lainez, C.; de la Mora-de la Mora, I.; Enríquez-Flores, S.; García-Torres, I.; Flores-López, L.A.; Gutiérrez-Castrellón, P.; de Vos, P.; López-Velázquez, G. The Giardial Arginine Deiminase Participates in Giardia-Host Immunomodulation in a Structure-Dependent Fashion via Toll-like Receptors. Int. J. Mol. Sci. 2022, 23, 11552. https://doi.org/10.3390/ijms231911552
Fernández-Lainez C, de la Mora-de la Mora I, Enríquez-Flores S, García-Torres I, Flores-López LA, Gutiérrez-Castrellón P, de Vos P, López-Velázquez G. The Giardial Arginine Deiminase Participates in Giardia-Host Immunomodulation in a Structure-Dependent Fashion via Toll-like Receptors. International Journal of Molecular Sciences. 2022; 23(19):11552. https://doi.org/10.3390/ijms231911552
Chicago/Turabian StyleFernández-Lainez, Cynthia, Ignacio de la Mora-de la Mora, Sergio Enríquez-Flores, Itzhel García-Torres, Luis A. Flores-López, Pedro Gutiérrez-Castrellón, Paul de Vos, and Gabriel López-Velázquez. 2022. "The Giardial Arginine Deiminase Participates in Giardia-Host Immunomodulation in a Structure-Dependent Fashion via Toll-like Receptors" International Journal of Molecular Sciences 23, no. 19: 11552. https://doi.org/10.3390/ijms231911552