Exercise improves intestinal IgA production by T-dependent cell pathway in adults but not in aged mice.

Introduction: Hypermutated high-affinity immunoglobulin A (IgA), neutralizes toxins and drives the diversification of bacteria communities to maintain intestinal homeostasis although the mechanism underlies the impact of moderate aerobic exercise (MAE) on the IgA-generation via T-dependent (TD) is not fully know. Therefore, the aim of this study was to determine the effect of long-time MAE on the production of IgA through the TD pathway in Peyer´s patches of the small intestine from aged mice. Methods: MAE protocol consisted of twenty 3-month-old (young) BALB/c mice running in an endless band at 0° inclination and a speed of 10 m/h for 5 days a week and resting 2 days on the weekend until reaching 6-month-old (adulthood, n=10) or 24-month-old (aging, n=10). Groups of young, adult, or elderly mice were included as sedentary controls (n=10/per group). At 6 or 24 months old, all were sacrificed, and small intestine samples were dissected to prepare intestinal lavages for IgA quantitation by ELISA and to obtain suspensions from Peyer´s patches (PP) and lamina propria (LP) cells for analysis of T, B, and plasma cell subpopulations by flow cytometry and mRNA analysis expression by RT-qPCR of molecular factors related to differentiation of B cells to IgA+ plasma cells, class switch recombination, and IgA-synthesis. Statistical analysis was computed with two-way ANOVA (factor A=age, factor B=group) and p<0.05 was considered for statistically significant differences. Results: Compared to age-matched sedentary control, in exercised elderly mice, parameters were either increased (IgA concentration, IL-21, IL-10 and RDH mRNA expression), decreased (α-chain mRNA, B cells, mIgA+ B cells, mIgM+ B cells and IL-4 mRNA) or unchanged (PP mIgA+ plasmablasts and LP cyt-IgA+ plasma cells). Regarding the exercised adult mice, they showed an up-modulation of IgA-concentration, mRNA expression IL-21, IL-10, and RDH and cells (PP B and T cells, mIgM+ plasmablasts and LP cyt-IgA+plasma cells). Conclusion: Our findings suggest that MAE restored the IgA production in adult mice via the TD cell pathway but does not in aged mice. Other studies are necessary to know in more detail the impact of long-time MAE on the TD pathway to produce IgA in aging.

Active fractions of mannoproteins derived from yeast cell wall stimulate innate and acquired immunity of adult and elderly dogs.

Nutritional intervention in older dogs aims to increase lifespan and improve life quality as well as delay the development of diseases related to ageing. It is believed that active fractions of mannoproteins (AFMs) obtained through extraction and fractionation of yeast cell walls (Saccharomyces cerevisiae) may beneficially modulate the immune system. However, studies that have evaluated this component and the effects of ageing on the immune system of dogs are scarce. This study aimed to evaluate the immunological effects of AFMs in adult and elderly dogs. Three extruded iso-nutrient experimental diets were formulated: without addition of AFM (T0); with AFM at 400 mg/kg (T400); and with AFM at 800 mg/kg (T800). Thirty-six beagle dogs were used, and six experimental treatments, resulting in combinations of age (adult and elderly) and diet (T0, T400, and T800), were evaluated. On days zero, 14, and 28, blood samples were obtained for leucocyte phenotyping and phagocytosis assays. On days zero and 28, a lymphoproliferation test, quantification of reactive oxygen (H2O2) and nitrogen (NO) intermediate production, evaluation of faecal immunoglobulin A (IgA) content, and a delayed cutaneous hypersensitivity test (DCHT) were performed. Statistical analyses were performed with SAS software. Repeated measure variance analyses were performed, and means were compared by the Tukey test. Values of P ≤ 0.05 were considered significant, and values of P ≤ 0.10 were considered tendencies. Dogs fed T400 tended to have higher neutrophilic phagocytic activity than dogs fed T800 (P = 0.073). Regarding reactive oxygen intermediates, bacterial lipopolysaccharide (LPS)-stimulated neutrophils from animals that were fed T400 had a tendency to produce more H2O2 than those from animals fed the control diet (P = 0.093). Elderly dogs, when compared to adult dogs, had lower absolute T and B lymphocyte counts, lower auxiliary T lymphocyte counts, and higher cytotoxic T lymphocyte counts (P < 0.05). A significant effect of diet, age, and time with saline inoculation was noted for the DCHT. There was no effect of diet or age on faecal IgA content in dogs. This study suggests beneficial effects of mannoproteins on the specific and nonspecific immune responses in adult and elderly dogs.

Participación de las células Th17 en la patogenia de la infección por el virus de la inmunodeficiencia humana de tipo 1 / Th17 cells involvement in the pathogenesis of the human immunodeficiency virus type 1

La infección por el VIH-1 se caracteriza por la eliminación de linfocitos T CD4+, particularmente en la mucosa gastrointestinal, que favorece la traslocación microbiana y la hiperactivación inmunitaria, principal mecanismo patogénico en esta infección. Las células Th17 son una subpoblación proinflamatoria de linfocitos CD4+, que producen IL-17, IL-21 e IL-22, y son importantes en la respuesta antimicrobiana, principalmente en el sistema gastrointestinal, donde promueven la restauración de la mucosa. Aunque su eliminación se ha asociado con progresión de la infección por el VIH-1 y por el virus de la inmunodeficiencia de los simios, y han sido descritas como deletérea en autoinmunidad. Su papel en la patogenia de la infección por el VIH-1 no está claramente establecido. Considerando su capacidad funcional, las células Th17 podrían tener un impacto dual, dependiendo de la fase de la infección en que se encuentre el individuo. Actualmente, hay más información que sugiere que estas células tienen un papel benéfico al promover la recuperación de la mucosa intestinal y disminuir la traslocación microbiana, así como la hiperactivación inmunitaria. Sin embargo, su papel patogénico, particularmente promoviendo la replicación viral mediante la producción de citocinas proinflamatorias, no debe descartarse. En esta revisión, se presentan los datos científicos disponibles del efecto de las células Th17 en la patogenia de la infección por el VIH-1.

HIV-1 infection is characterized by a gradual decrease of the immunological competence and a massive depletion of CD4+ T cells, particularly in gut-associated lymphoid tissue, which leads to microbial translocation, contributing to immune hyperactivation, the main pathogenic mechanism during HIV-1 infection. Th17 cells are a proinflammatory CD4+ T cell subset, which produce IL-17, IL-21 and IL-22 and play a pivotal role in host defense, mainly in the gastrointestinal tissue, where they promote antimicrobial responses and gut mucosa restoration. Although Th17 depletion is a hallmark of the progression of the simian and human immunodeficiency viral infections and they have been involved in the pathogenic process in some autoimmune diseases, the role of these cells during HIV-1 infection is not completely understood. Considering their functional potential, Th17 cells could have a dual role, depending on the stage of HIV infection a patient has reached. Currently, most evidence suggests that Th17 cells have a beneficial role by promoting gut mucosa recovery, preventing microbial translocation and decreasing immune hyperactivation. However, the pathogenic role of these cells, particularly, increasing viral replication through the production of inflammatory cytokines should not be ruled out. In this review, scientific evidence regarding the role of Th17 on the pathogenesis of HIV infection is discussed.