Helicobacter pylori Neutrophil Activating Protein (HP-NAP) Enhances the Anti-Leishmanial Activity of Canine Macrophages Against Leishmania infantum

Leishmania infantum is the etiological agent of visceral leishmaniasis (VL) and is linked to cases of cutaneous leishmaniasis in dogs. Dogs often develop severe systemic disease and serve as the primary reservoir of L. infantum. Although several vaccine candidates are under development, no vaccine for visceral leishmaniasis has been approved for human use to date. Chemotherapeutic treatment is hampered by toxicity, cost, and the emergence of parasite-resistant strains. Immunotherapy, combining chemotherapy with modulation of Th1 responses, is a promising therapeutic approach. Helicobacter pylori neutrophil-activating protein (HP-NAP), an immunomodulatory protein from Helicobacter pylori, is known to promote Th1 immune responses. A Th1 response activates macrophage promoting parasite killing, while a Th2 response favors disease progression. Macrophages are central for infection, either eliminating parasites (Th1 response) or supporting their persistence (Th2 response). IL-12 is a crucial cytokine in driving Th1 immunity and counteracting Th2 responses. We therefore investigated the role of HP-NAP in an in vitro model of L. infantum macrophage infection. Canine monocyte-derived macrophages from seven dogs were incubated with L. infantum promastigotes. More than 85% of macrophages from all donors were infected, with approximately seven amastigotes per cell. HP-NAP treatment significantly reduced all infection parameters and induced IL-12 production. Collectively, these findings suggest that HP-NAP may represent a promising candidate for adjuvant immunotherapies and vaccine development against L. infantum.