Paratuberculosis vaccination induces a phenotype consistent with trained immunity in bovine neutrophils

Vaccination decreases bacterial shedding and reduces the incidence and severity of infection by Mycobacterium avium subsp. paratuberculosis (Map), the causative agent of paratuberculosis (PTB), a chronic granulomatous enteritis that economically impacts the dairy industry. An inactivated Map vaccine exhibits features suggestive of trained immunity in cattle, along with enhanced neutrophil (PMN) activation in rabbits. Although PMNs from healthy cattle exhibit antimicrobial effects against Map, the impact of vaccination on bovine PMN function remains undetermined. This study has further explored the mechanisms of trained immunity mediated by PMNs elicited by this vaccine in calves. PMN mediated phagocytosis, ROS production and NET release showed a significant increase in vaccinated calves upon stimulation in ex vivo assays. Furthermore, PMNs from vaccinated animals exhibited decreased motility that was partially restored upon ex vivo stimulation with Map. Upregulation of phagocytosis receptors such as TREM2 and PBDL1, genes related to NETosis TREM2, LYZ and F13A1 and downregulation of genes involved in chemotaxis, adhesion, and motility in vaccinated animals support these findings. Altogether, the data indicate that this inactivated Map vaccine induces changes consistent with trained immunity in calves.