Abstract
A stronger Th1 (cellular) immune response in canine leishmaniosis (CanL) leads to a better prognosis. Dietary nucleotides plus AHCC® have shown beneficial effects in dogs with clinical leishmaniosis and in clinically healthy Leishmania-infected dogs. The potential leishmanicidal activity of nucleotides and AHCC was assessed by quantifying nitric oxide (NO) production and replication of parasites. Their effects on lymphocyte proliferation were studied with and without soluble Leishmania infantum antigen (SLA) stimulation. Cytokine level variations were assessed using naïve and L. infantum-infected macrophages/lymphocytes cocultures. Promastigotes and amastigotes proliferation and NO macrophage production were not directly affected. Lymphocyte proliferation was significantly enhanced by nucleotides, AHCC, and their combinations only after SLA stimulation. Nucleotides and AHCC significantly increased the production of IL-1β, IL-2, IL-5, IL-9, IL-10, and IL-12 by naïve immune cells. In naïve and L. infantum-infected macrophage/lymphocyte cocultures, nucleotides with or without AHCC led to significant increases in IFN-γ and TNF-α. Given that these cytokines are involved in the effective Th1 immune response against Leishmania parasites, these mechanisms of action could explain the previously reported in vivo clinical efficacy of such combination and further support the use of nucleotides with or without AHCC in the management of CanL patients.
Highlights
Unicellular flagellates of the family Trypanosomatidae are obligatory parasites of invertebrates, vertebrates, and plants
The production of nitric oxide (NO) by macrophages was not altered following the application of compounds alone or with any of the combinations suggesting that the in vivo efficacy of nucleotides plus AHCC in canine leishmaniosis (CanL) patients previously reported [24,25] probably occurs through a different mechanism of action
No in vitro changes were observed with the compounds alone or with any of the combinations on parasites growth, indicating that nucleotides and AHCC do not elicit a direct activity against the parasites
Summary
Unicellular flagellates of the family Trypanosomatidae are obligatory parasites of invertebrates, vertebrates, and plants. This family includes pathogens responsible for African sleeping sickness, Chagas’ disease, and leishmaniases, among others. The subfamily Leishmaniinae includes monoxenous parasites of insects and dixenous parasites of insects and vertebrates (genera Leishmania, Paraleishmania and ‘Endotrypanum’) [1,2]. Leishmaniasis is a complex of infectious diseases caused by protozoan parasites belonging to species of the genus Leishmania. These diseases affecting humans and several wild and domestic mammals are transmitted by Diptera arthropods belonging to genus Lutzomyia in Molecules 2020, 25, 3918; doi:10.3390/molecules25173918 www.mdpi.com/journal/molecules. The clinical spectrum of the disease is largely dependent on the infecting species and the intrinsic characteristics of the host, varying from the benign cutaneous forms to the most severe form, visceral leishmaniasis, which is fatal if left untreated [4]
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