Exploring the immunosuppressive potential of venom-derived molecules (#359)
Venomous creatures produce lethal cocktails of potent, specific, and fast-acting molecules ready for delivery by bite or sting. Venoms can contain hundreds of unique molecules, each with specialised mechanisms of action. In concert venoms rapidly disrupt vital biological processes in prey and predators. Ironically, the same characteristics that make venom biologically effective presents an ideal platform for the exploration of novel therapeutics and immunological pathways. This study involved identifying snake venom components with potent immune modulating activity for potential development of drugs for the treatment of chronic inflammatory diseases. The effects of venom on human leukocytes were assessed using multiplex bead-based flow cytometry, proliferation assays and cell viability assays. The venoms identified as immunosuppressive were fractionated using RP-HPLC and screened for activity against mitogen-induced activation. The results showed that specific venom fractions significantly inhibited IL-2, IFNγ, and TNFα release when primary leukocytes were stimulated with either Cell Stimulation Cocktail or CD3/CD28 activation beads. Interestingly, no change was observed in the myeloid compartment in response to lipopolysaccharide activation. Further, although venom treatment reduced T-cell secreted cytokines to control levels, no significant inhibition of proliferation or reduction in cell viability was found suggesting these activation pathways are distinct in humans. Collectively, these data reveal novel venom-derived molecules specifically target and deactivate T-cells and could potentially be used to control or fine-tune the function of the human immune system.