Besnoitia besnoiti-induced neutrophil extracellular traps (NETs) : metabolic signature, signaling pathways, receptors and implications on pathogenesis

Abstract

Besnoitia besnoiti is an apicomplexan parasite responsible for bovine besnoitiosis, a debilitating disease in cattle resulting in local and systemic clinical signs with detrimental effects on reproductive performance and productivity in livestock. Fast-replicating tachyzoites and slowly proliferating bradyzoites elicit an excessive host innate immune response, mainly by activated polymorphonuclear neutrophils (PMN), which extrude neutrophil extracellular traps (NETs) as a defense mechanism. These PMN-derived structures, composed principally of DNA, histones, and peptides, play a crucial role not only in parasite entrapment but also in NET-associated endothelial damage, thereby most likely contributing to the pathogenesis of this neglected cattle parasitosis. Uncontrolled production of NETs or their inadequate removal may perpetuate an inflammatory environment in the vasculature and epidermis. Thus, novel alternative treatment of animals with chronic bovine besnoitiosis displaying severe clinical manifestations such as hyperkeratosis, vulvovaginitis and orchitis, could be considered for future study to either hampering NETs release or reducing NETs concentrations in affected tissues. Since effective treatments and control strategies for bovine besnoitiosis do not yet exist, this review serves as a guide for further research on the metabolic signature, signaling pathways, receptors, and pathogenesis of B. besnoiti-triggered NETs formation, providing insights into potential therapeutic approaches to avoid excessive NETs extrusion.