No evidence of neutrophil response modulation in goats after immunization against paratuberculosis with a heat-inactivated vaccine

18 páginas, 6 figuras.

Neutrophils are believed to play a role in the initial stages of paratuberculosis, and it has recently been demonstrated that vaccination can modulate their function via priming or through epigenetic and metabolic reprogramming (training). Modulation of the neutrophil response against Mycobacterium avium subspecies paratuberculosis (Map) through vaccination has been demonstrated in a rabbit model but not in ruminants. Therefore, in the present work, the effect of vaccination on the response of caprine neutrophils against Map was studied. Neutrophils were isolated from non-vaccinated (n = 7) and Gudair®-vaccinated goat kids (n = 7), before vaccination and 30 days post-vaccination. Then, several neutrophil functions were quantified ex vivo: cell-free and anchored neutrophil extracellular trap (NET) release, phagocytosis, and the differential expression of several cytokines and TLR2. The induction of cell-free NETosis and TLR2 expression by Map is reported for the first time. However, vaccination showed no significant effect on any of the functions studied. This suggests that the protection conferred by Gudair® vaccination is based on mechanisms that are independent of the neutrophil function modulation. Further research into the impact of alternative vaccination strategies or the paratuberculosis infection stage on ruminant neutrophil function could provide valuable insights into its role in paratuberculosis.

This work was funded by the projects RTI2018-099496-B-I00 and PID2021-125807OB-C21, from the “Agencia Estatal de Investigación” of the Spanish Ministry of Science and Innovation. Miguel Criado Boyero acknowledges the receipt of a pre-doctoral grant (PRE2019-087309) from MCIN/AEI/10.13039/501100011033 and FSE “El FSE invierte en tu futuro”. Pedro Mendívil Gutiérrez acknowledges the receipt of a pre-doctoral grant funded by Junta de Castilla y Leon and FSE (grant no. LE175-22).

Peer reviewed