Nutritional Modulation of the Immune Response Mediated by Nucleotides in Canine Leishmaniosis

Leishmaniasis is an emerging, uncontrolled, and neglected zoonotic disease. Climate change is contributing to its ongoing global expansion. The dog is the main reservoir; hence the importance of implementing effective treatment, prevention, and control measures in this animal species to protect public health. However, although the standard treatment for canine leishmaniosis (CanL) is effective, it does not provide full parasitological clearance, and side effects and drug resistance have been described. The host’s immune system plays a key role in the establishment and evolution of leishmaniasis. Dietary nucleotides modulate the immune response and, given their reported efficacy and safety in sick and clinically healthy Leishmania-infected dogs and because they represent a sustainable option with no associated side effects or resistance, they could be included within the prevention, treatment, and control strategies for leishmaniasis. This article briefly summarizes the scientific literature on CanL management, including unresolved issues, and reviews the scientific evidence on immunomodulatory effects of dietary nucleotides in different animal species. It also proposes a CanL management algorithm, including nucleotides. It is concluded that nutritional modulation of the immune response with nucleotides can contribute to better management of leishmaniasis following a One Health approach, especially in the COVID-19 era.

Dietary Nucleotides Retard Oxidative Stress-Induced Senescence of Human Umbilical Vein Endothelial Cells

Several lines of evidence suggest an inhibitory role of dietary nucleotides (NTs) against oxidative stress and inflammation, which promote senescence in age-associated cardiovascular diseases. We sought to test whether the dietary NTs could retard the hydrogen peroxide (H2O2)-induced senescence of human umbilical vein endothelial cells (HUVECs) and to elucidate the efficiency of different NTs as well as the potential mechanism. Senescence was induced in HUVECs by 4 h exposure to 200 µM H2O2 and was confirmed using senescence-associated-β-galactosidase staining (SA-β-gal), cell viability, and Western blot analyses of p16INK4A and p21Waf1/Cip1 after 24 h administration of growth medium. We find that NTs retards oxidative stress-induced HUVECs senescence, as shown by a lower percentage of SA-β-gal-positive cells, lower expression of p16INK4A, and p21Waf1/Cip1 as well as higher cell viability. GMP100 was the most excellent in delaying HUVECs senescence, which was followed by the NTs mixture, NMN, CMP50, and UMP50/100, while AMP retards HUVECs senescence by specifically reducing p15INK4b expression. NTs all have significant anti-inflammatory effects; AMP and CMP were more prominent in restoring mitochondrial function, GMP and CMP were more competent at eliminating ROS and MDA, while AMP and UMP were more efficient at enhancing antioxidant enzyme activity. The role of the NTs mixture in retarding HUVECs senescence is full-scaled. These results stated that the mechanisms of NTs retarding HUVECs senescence could be related to its antioxidant and anti-inflammation properties promoting cell proliferation and protecting mitochondrial function activities.

Effects of dietary nucleotides and cationic peptides on vaccination response in cats

Modulation of the immune system through nutrition is the aim of many studies. As the induction of a rapid onset of immunity in cats is often critical, the objective of this study was to evaluate the effects of orally administered dietary nucleotides and cationic peptides, on the vaccination response in cats. The cats were allocated to two groups: Group A (n = 8) was fed a diet with dietary nucleotides and cationic peptides for ninety-two days, and Group C (n = 8) was fed a diet without the nucleotides and cationic peptides. The cats were vaccinated against feline herpesvirus 1 (FHV-1), feline calicivirus (FCV) and feline panleukopenia virus (FPV). The proliferation activity of lymphocytes and antibody response after vaccination were evaluated using ELISA kits. Comparing the two groups, a significant increase in the proliferation activity of the lymphocytes (P < 0.01) was observed in Group A, as well as a significant increase in the antibody titres after vaccination against feline herpesvirus (P < 0.05; P < 0.001), feline calicivirus (P < 0.01; P < 0.001) and feline panleukopenia virus (P < 0.01; P < 0.001). Protective levels of the antibodies were reached significantly earlier in Group A than in Group C. In conclusion, dietary nucleotides and cationic peptides have a positive effect on the lymphocyte proliferation and antibody production after vaccination against FHV-1, FCV and FPV in cats. Therefore, we assume that they can be used as a suitable immunostimulatory substance in feline practice.

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

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.

The role of oral supplementation with immunonutrients in the inflammatory response in patients with COVID-19

Introduction: The SARS-CoV-2 related coronavirus has spread to almost every country, causing the COVID-19. The severity of COVID-19 is based on the inflammation caused by the cytokine storm. Inflammatory markers suggest a molecular explanation for the occurrence of severe disease and represent a possible treatment. Objective: This review aims to analyse the plausibility of using oral supplementation with immunonutrients. Discussion: Immunonutrition studies the interactions between nutrition, the immune system, infection, and inflammation of tissues. Arginine is a fundamental amino acid in processes of metabolic stress. Its deficiency implies in the capacity of immune response. ω-3 fatty acids demonstrated improved lung compliance, oxygenation, mechanical ventilation time and intensive care unit stay in patients with acute respiratory distress syndrome. Essential for cell-mediated immunity and T lymphocyte function, dietary nucleotides have been shown to improve the cytotoxicity of natural killer cells. Considering that the inversely proportional relationship between presence of IL-6 and TNF-α and the function of T cells is well established in patients with COVID-19, this reinforces the idea that the release control of these biomarkers can be a way to treat this disease. Conclusion: In this scenario, this review raises the possibility of using immunonutrition to improve immune response of individuals affected by COVID-19.