The Kiss of (Cell) Death: When Venom Turns a Victim’s Immune System Against its Host

A necrotic wound from a cobra snake bite. Photo: NUI Galway/Shutterstock
Feb 28 2019 Posted: 16:51 GMT

Researchers from the Ryan Institute at NUI Galway have just published a review paper which draws a link between the immune system and the development of debilitating necrotic skin wounds after envenomation (a bite or sting) by a broad range of venomous animals. Once confirmed by future experiments, it will have deep implications on how life-threatening necrotic wounds following envenomations by snakes, wasps, bees, ants, spiders, scorpions and jellyfish, will be treated by clinicians. This could impact some 500,000 patients every single year, all around the world. The review has just been published (26 February) in the journal Clinical Toxicology.

Envenomations by snakes, wasps, bees, ants, spiders, scorpions or jellyfish are common throughout the world. In most cases, the venom impacts the victim’s nervous system, causing burning pain, stiffness and difficulty breathing. Occasionally, victims also develop necrotic wounds where bitten or stung, which are often inconsistent with the known activity of some types of venom. Those seemingly inexplicable wounds are notoriously difficult to treat, and sometimes result in deep scars, debilitating chronic pain and amputations.

In addition to direct lytic activity of the venom, necrotic manifestations can also be either enhanced by, or caused solely by the victim’s own immune system in response to the presence of venom toxins through activated pathways of regulated cell death.  

John Dunbar, lead author of the study and doctoral student at the Ryan Institute in NUI Galway, said: “Venom-induced necrosis is a well-known fact and most prevalent in Snakebite victims. Surprisingly, very little has been done to understand the mechanisms that drives necrosis, despite promising results from two particular studies published around two decades ago. Necrosis is something we usually associate with an attack on our cells by external forces.  However, in recent years, advances in biochemistry and immunology have helped identify and characterise a number of cell death pathways that are regulated internally by the cells own proteins. We’ve re-analysed those venom-related studies in light of these recent advances.”

Dr Michel Dugon from the Ryan Institute at NUI Galway, says: “Envenomations remain a leading cause of deaths and injuries around the world. Venomous animals kill over 150,000 and maim over half a million people every single year around the globe. Identifying and targeting specific inflammatory pathways to regulated cell death (try to determine the exact physiological events that cascade in a person’s immune system after a venomous sting or bite), may significantly reduce the severity of symptoms experienced by the victims. It is something that we will aim to address in the very near future.”

This study suggests that in addition to the current therapies that specifically target the venom, further research should examine immune-suppression therapies as a way to treat victims.

To read the full report in the Clinical Toxicology journal, visit: https://doi.org/10.1080/15563650.2019.1578367

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