Venom of the red-bellied black snake Pseudechis porphyriacus shows immunosuppressive potential

Ryan, Rachael Y.M., Lutzky, Viviana P., Herzig, Volker, Smallwood, Taylor B., Potriquet, Jeremy, Wong, Yide, Masci, Paul, Lavin, Martin F., King, Glenn F., Lopez, J. Alejandro, Ikonomopoulou, Maria P., and Miles, John J. (2020) Venom of the red-bellied black snake Pseudechis porphyriacus shows immunosuppressive potential. Toxins, 12 (11). 674.

[img]
Preview
PDF (Published Version) - Published Version
Available under License Creative Commons Attribution.

Download (911kB) | Preview
View at Publisher Website: https://doi.org/10.3390/toxins12110674
 
1
18


Abstract

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 (Pseudechis porphyriacus) 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 P. porphyriacus venom may be potential drug leads for T cell-associated conditions such as graft versus host disease, rheumatoid arthritis, and inflammatory bowel disease.

Item ID: 66039
Item Type: Article (Research - C1)
ISSN: 2072-6651
Keywords: Pseudechis porphyriacus; red-bellied black snake; snake venom; immunosuppression; TNF; CD4+ T cells
Copyright Information: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open accessarticle distributed under the terms and conditions of the Creative Commons Attribution(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Funders: Australian Government (AG), AMAROUT Marie Curie (AMC), Regional Madrid Government (RMG), Career Development Fellowship (CDF), Principal Research Fellowship (PRF), Australian National Health and Medical Research Council (NHMRC)
Projects and Grants: AG Research Training Program, AMC program N 291803-AMAROUT II, RMG TALENTO program 2018-T1/BIO-11262, CDF APP1131732, PRF APP1136889
Date Deposited: 19 Feb 2021 05:20
FoR Codes: 31 BIOLOGICAL SCIENCES > 3101 Biochemistry and cell biology > 310199 Biochemistry and cell biology not elsewhere classified @ 100%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280103 Expanding knowledge in the biomedical and clinical sciences @ 100%
Downloads: Total: 18
Last 12 Months: 18
More Statistics

Actions (Repository Staff Only)

Item Control Page Item Control Page