No Evidence of Neutrophil Response Modulation in Goats after Immunization against Paratuberculosis with a Heat-Inactivated Vaccine

Abstract

Simple Summary Among other limitations, the currently available vaccines against paratuberculosis do not offer complete protection against infection, and further vaccine development is limited by a lack of understanding of the mechanisms behind vaccine-induced protection. In this regard, the most recent studies have demonstrated that neutrophil function can be modulated through vaccination against several pathogens, including Mycobacterium avium subspecies paratuberculosis (Map). However, this modulation has not been described in ruminants, which are the natural hosts of Map. In the present work, the effect of vaccination on the neutrophil response against Map was assessed in goats using the only available vaccine against small ruminant paratuberculosis, Gudair®. No differences were found in the ex vivo response of neutrophils isolated from non-vaccinated and vaccinated animals, which suggests that the protection conferred by this heat-inactivated vaccine is based on mechanisms other than neutrophil modulation. It is possible that neutrophil modulation depends largely on the intensity of the immune response elicited by the vaccine employed or the antigen dose, as the previous reports which observed this modulation used live attenuated vaccines or were performed in laboratory animals using experimental vaccines. Abstract 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.