Venom of the Red-Bellied Black Snake <i>Pseudechis porphyriacus</i> Shows Immunosuppressive Potential
Venoms act with remarkable specificity upon a broad diversity of physiological targets. Venoms are composed of proteins, peptides, and small molecules, providing the foundation for the development of novel therapeutics. This study assessed the effect of venom from the red-bellied black snake (<i&...
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doaj-4c8e9527220b430a98472d3e3d68b10c2020-11-25T03:38:35ZengMDPI AGToxins2072-66512020-10-011267467410.3390/toxins12110674Venom of the Red-Bellied Black Snake <i>Pseudechis porphyriacus</i> Shows Immunosuppressive PotentialRachael Y. M. Ryan0Viviana P. Lutzky1Volker Herzig2Taylor B. Smallwood3Jeremy Potriquet4Yide Wong5Paul Masci6Martin F. Lavin7Glenn F. King8J. Alejandro Lopez9Maria P. Ikonomopoulou10John J. Miles11Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, AustraliaQIMR Berghofer Medical Research Institute, Herston, QLD 4006, AustraliaInstitute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, AustraliaQIMR Berghofer Medical Research Institute, Herston, QLD 4006, AustraliaAB SCIEX, Herston, QLD 4006, AustraliaAustralian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, AustraliaTranslational Research Institute, Brisbane, QLD 4102, AustraliaCentre for Clinical Research, The University of Queensland, Brisbane, QLD 4029, AustraliaInstitute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, AustraliaSchool of Environment and Sciences, Griffith University, Nathan, QLD 4111, AustraliaQIMR Berghofer Medical Research Institute, Herston, QLD 4006, AustraliaAustralian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, AustraliaVenoms act with remarkable specificity upon a broad diversity of physiological targets. Venoms are composed of proteins, peptides, and small molecules, providing the foundation for the development of novel therapeutics. This study assessed the effect of venom from the red-bellied black snake (<i>Pseudechis porphyriacus</i>) on human primary leukocytes using bead-based flow cytometry, mixed lymphocyte reaction, and cell viability assays. We show that venom treatment had a significant immunosuppressive effect, inhibiting the secretion of interleukin (IL)-2 and tumor necrosis factor (TNF) from purified human T cells by 90% or greater following stimulation with mitogen (phorbol 12-myristate 13-acetate and ionomycin) or via cluster of differentiation (CD) receptors, CD3/CD28. In contrast, venom treatment did not inhibit TNF or IL-6 release from antigen-presenting cells stimulated with lipopolysaccharide. The reduced cytokine release from T cells was not associated with inhibition of T cell proliferation or reduction of cell viability, consistent with an anti-inflammatory mechanism unrelated to the cell cycle. Deconvolution of the venom using reverse-phase HPLC identified four fractions responsible for the observed immunosuppressive activity. These data suggest that compounds from <i>P. porphyriacus</i> venom may be potential drug leads for T cell-associated conditions such as graft versus host disease, rheumatoid arthritis, and inflammatory bowel disease.https://www.mdpi.com/2072-6651/12/11/674<i>Pseudechis porphyriacus</i>red-bellied black snakesnake venomimmunosuppressionTNFCD4<sup>+</sup> T cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rachael Y. M. Ryan Viviana P. Lutzky Volker Herzig Taylor B. Smallwood Jeremy Potriquet Yide Wong Paul Masci Martin F. Lavin Glenn F. King J. Alejandro Lopez Maria P. Ikonomopoulou John J. Miles |
spellingShingle |
Rachael Y. M. Ryan Viviana P. Lutzky Volker Herzig Taylor B. Smallwood Jeremy Potriquet Yide Wong Paul Masci Martin F. Lavin Glenn F. King J. Alejandro Lopez Maria P. Ikonomopoulou John J. Miles Venom of the Red-Bellied Black Snake <i>Pseudechis porphyriacus</i> Shows Immunosuppressive Potential Toxins <i>Pseudechis porphyriacus</i> red-bellied black snake snake venom immunosuppression TNF CD4<sup>+</sup> T cells |
author_facet |
Rachael Y. M. Ryan Viviana P. Lutzky Volker Herzig Taylor B. Smallwood Jeremy Potriquet Yide Wong Paul Masci Martin F. Lavin Glenn F. King J. Alejandro Lopez Maria P. Ikonomopoulou John J. Miles |
author_sort |
Rachael Y. M. Ryan |
title |
Venom of the Red-Bellied Black Snake <i>Pseudechis porphyriacus</i> Shows Immunosuppressive Potential |
title_short |
Venom of the Red-Bellied Black Snake <i>Pseudechis porphyriacus</i> Shows Immunosuppressive Potential |
title_full |
Venom of the Red-Bellied Black Snake <i>Pseudechis porphyriacus</i> Shows Immunosuppressive Potential |
title_fullStr |
Venom of the Red-Bellied Black Snake <i>Pseudechis porphyriacus</i> Shows Immunosuppressive Potential |
title_full_unstemmed |
Venom of the Red-Bellied Black Snake <i>Pseudechis porphyriacus</i> Shows Immunosuppressive Potential |
title_sort |
venom of the red-bellied black snake <i>pseudechis porphyriacus</i> shows immunosuppressive potential |
publisher |
MDPI AG |
series |
Toxins |
issn |
2072-6651 |
publishDate |
2020-10-01 |
description |
Venoms act with remarkable specificity upon a broad diversity of physiological targets. Venoms are composed of proteins, peptides, and small molecules, providing the foundation for the development of novel therapeutics. This study assessed the effect of venom from the red-bellied black snake (<i>Pseudechis porphyriacus</i>) on human primary leukocytes using bead-based flow cytometry, mixed lymphocyte reaction, and cell viability assays. We show that venom treatment had a significant immunosuppressive effect, inhibiting the secretion of interleukin (IL)-2 and tumor necrosis factor (TNF) from purified human T cells by 90% or greater following stimulation with mitogen (phorbol 12-myristate 13-acetate and ionomycin) or via cluster of differentiation (CD) receptors, CD3/CD28. In contrast, venom treatment did not inhibit TNF or IL-6 release from antigen-presenting cells stimulated with lipopolysaccharide. The reduced cytokine release from T cells was not associated with inhibition of T cell proliferation or reduction of cell viability, consistent with an anti-inflammatory mechanism unrelated to the cell cycle. Deconvolution of the venom using reverse-phase HPLC identified four fractions responsible for the observed immunosuppressive activity. These data suggest that compounds from <i>P. porphyriacus</i> venom may be potential drug leads for T cell-associated conditions such as graft versus host disease, rheumatoid arthritis, and inflammatory bowel disease. |
topic |
<i>Pseudechis porphyriacus</i> red-bellied black snake snake venom immunosuppression TNF CD4<sup>+</sup> T cells |
url |
https://www.mdpi.com/2072-6651/12/11/674 |
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