Animal toxins and NETosis: A new frontier in innate immune modulation

Abstract

Neutrophil extracellular traps are molecular structures that play a dual role in host defense and pathology. While NETs effectively capture and neutralize pathogens, excessive or dysregulated NET formation contributes to autoimmune and inflammatory disorders. Animal venoms contain bioactive molecules that can modulate neutrophil functions, including NETosis. They are capable of inducing, inhibiting, or degrading NETs through different mechanisms, such as signaling pathway modulation, or direct DNA hydrolysis. Such effects not only shape the course of envenomation but also reveal novel pathways of innate immune regulation. This review summarizes current knowledge on NET biogenesis, function, and pathological implications, and highlights how animal toxins influence NET formation. We further discuss the therapeutic and biotechnological potential of these molecules as tools to modulate neutrophil-driven inflammation in conditions such as sepsis, cancer, and autoimmunity. By integrating insights from immunology and toxinology, this work points to animal venoms as a promising frontier for the discovery of immunomodulatory agents targeting NETs.