Nitric oxide production by macrophages of dogs vaccinated with killed Leishmania infantum promastigotes

Resume Human visceral leishmaniosis is endemic in Southern Italy, where the dog is the main reservoir of viscerotropic strains of Leishmania infantum . The release of nitric oxide (NO) by interferon (IFN)-γ-activated macrophages is an important leishmanicidal mechanism in several animal species. In this work NO production, phagocytosis and killing capacity of monocyte-derived dog macrophages were evaluated in vitro before and after administration of a vaccine composed of killed Leishmania infantum promastigotes. Moreover, IFN-γ content was measured in concanavalin A-activated dog peripheral blood mononuclear cell (PBMC) supernatants employed for macrophage stimulation. Phagocytosis, killing capacity and NO production by canine macrophages increased significantly 1 month after vaccine administration, and the increase also persisted 5 months later. In addition, the amount of IFN-γ in PBMC supernatants was significantly higher after vaccination. Overall, our results suggest the usefulness of evaluating the in vivo protective role of this promastigote preparation in dogs. La leishmaniose viscerale humaine est une maladie endemique au sud de l'Italie, le chien etant le principal reservoir de la souche viscerotropique de Leishmania infantum. La liberation de l'oxyde nitrique (NO) par de macrophages actives par l'interferon-gamma (IFN-γ) est un mecanisme leishmanicidal important chez plusieurs especes animales. Dans cette etude, la production d'oxyde nitrique, la phagocytose et la capacite de detruire, des macrophages canins derives de monocytes ont ete evalues in vitro, avant et apres l'administration d'un vaccin compose de Leishmania infantum promastigotes inactives. De plus, le contenu en IFN-γ a ete mesure dans des surnageant des cellules sanguines peripheriques mononucleaires (CSPM) du chien, activees par la concanavaline-A. Ces surnageants ont ete employes pour la stimulation des macrophages. La phagocytose, la capacite de detruire et la production de NO par les macrophages canins augmentent significativement un mois apres l'administration du vaccin, et cette augmentation persiste toujours cinq mois plus tard. De plus, apres vaccination la quantite d'IFN-γ libere dans les surnageants des CSPM etait plus elevee. L'ensemble des nos resultats suggerent la necessite d'evaluer le role protecteur in vivo de cette preparation promastigote chez le chien.