Nucleotides and AHCC Enhance Th1 Responses In Vitro in Leishmania -Stimulated/Infected Murine Cells

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 17; p. 3918
• Main Authors: Dea-Ayuela, María Auxiliadora, Segarra, Sergi, Serrano, Dolores R, Bolás-Fernández, Francisco
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.08.2020; MDPI
• Subjects: AHCC; Amastigotes; Animals; Antigens; Cells, Cultured; Cytokines; Cytokines - immunology; IL-1β; Immune response; Immune response (cell-mediated); Immune system; Immunity, Cellular; Infections; Interleukin 10; Interleukin 12; Interleukin 2; Interleukin 5; Interleukin 9; Leishmania; Leishmania infantum - drug effects; Leishmania spp; Leishmaniasis; Leishmaniasis - drug therapy; Lymphocytes; Lymphocytes T; Macrophages; Macrophages - immunology; Mice; Mice, Inbred BALB C; Nitric oxide; Nucleotides; Nucleotides - pharmacology; Nucleotides - therapeutic use; Parasites; Parasitic diseases; Polysaccharides - pharmacology; Promastigotes; Stimulation; Th1 Cells - immunology; Th1 response; Tumor necrosis factor-TNF; Tumor necrosis factor-α; γ-Interferon; Th1 response; promastigotes; amastigotes; mechanism of action; AHCC; cytokines; nucleotides; Leishmania spp
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25173918

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 -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 antigen (SLA) stimulation. Cytokine level variations were assessed using naïve and -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 -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 parasites, these mechanism 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.