In Vitro Activation of Macrophages by an MHC Class II-restricted Trichomonas Vaginalis TvZIP8-derived Synthetic Peptide

ABSTRACT

Background

Macrophages play an important role in the inflammatory response towards pathogens and their effector functions depend on the mode of activation which is mediated by recognition of pathogen-associated molecular patterns, as peptides. Trichomonas vaginalis provokes an inflammatory response in the host in which macrophages are the first line of defense. This study aimed to analyze the effect of a specific peptide derived from the transporter TvZIP8 of T. vaginalis on the activation of macrophages.

Methods

An in silico approach based on computational prediction of epitopes was applied to detect potential murine MHC class II-restricted peptides from TvZIP8 that can activate macrophages and the immunomodulatory activity was evaluated by in vitro stimulation of murine macrophages.

Results

Based on binding scores, one peptide denominated TvZIP8-pep was selected for further analysis. In vitro stimulation with synthetic TvZIP8-pep triggered on murine macrophages the NO and H₂O₂ production and an overexpression of iNOS and NOX-2 genes. Also, a significant increase of pro-inflammatory cytokines: IL-1β, IL-6, and TNF-α, as well as, overexpression of the TLR4, MyD88, and NF-κB genes and NF-κB activation were observed on macrophages after stimulation with TvZIP8-pep in vitro. Moreover, higher levels of IFN-γ were detected in co-cultures using CD4 + T cells with TvZIP8-pep-stimulated macrophages

Conclusion

These results support the potential of TvZIP8 as a promising antigen to stimulates a specific macrophage response against T. vaginalis, but further analyses are required to evaluate their possible potential as a novel antigen for immunodiagnosis and/or vaccine against trichomoniasis.

KEYWORDS:

• Macrophages
• immunomodulatory
• synthetic peptides
• Trichomonas vaginalis
• ZIP transporters

Acknowledgments

We thank to CONACYT for the scholarship awarded to E. Ceballos-Góngora.

Data availability statement

The data that support the conclusions of this study are included within the article and are available from the corresponding author upon request. https://ind01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fcorreouady-my.sharepoint.com%2F%3Af%3A%2Fg%2Fpersonal%2Fjulio_torres_correo_uady_mx%2FEgyLoHTG_StMupnpgu3Eu_MBxhtr7siaPciUJ_rB2PWnfQ%3Fe%3D2xLfIZ&data=02%7C01%7Csathyan.dhanasekaran%40integra.co.in%7C1a56bd8746044501877c08d8430a95f8%7C70e2bc386b4b43a19821a49c0a744f3d%7C0%7C0%7C637333060052697917&sdata=BJyq3YQ4X4dhEXy85pie67BF%2F3Ev76KXcDBa625wT7w%3D&reserved=0

Conflicts of interest statement

The authors declare no conflict of interest.

Additional information

Funding

This work was undertaken as part of a research project supported by Grant 237990 (to J.C. Torres-Romero) from Consejo Nacional de Ciencia y Tecnología (CONACYT), México.