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Background and purpose Brain derived neurotrophic factor ( BDNF) is suggested to play a neuroprotective role in multiple sclerosis ( MS). However, the BDNF response to long-term exercise in MS remains unknown. Our objective was to compare resting BDNF profiles of healthy controls ( HCs) and persons with relapsing−remitting MS ( RRMS) and to investigate the impact of a 24-week exercise intervention on serum BDNF release in MS. Methods At baseline, blood BDNF levels were assessed in MS ( n = 22, mean Expanded Disability Status Scale 2.6 ± 0.2, mean age 43 ± 2 years) and HCs ( n = 19, mean age 47 ± 1 year). Next, persons with MS were randomized to an exercise intervention group ( EX, n = 15) or a sedentary control group ( SED, n = 7) completing a 24-week randomized controlled trial. In persons with MS, muscle strength, exercise tolerance and body composition were assessed, as compliance measures, at baseline and after 24 weeks. Results At baseline, the BDNF concentration of persons with RRMS was 21% lower than HCs. Following 24 weeks of intervention, changes in BDNF concentrations differed significantly between EX and SED. In particular, within EX BDNF concentrations increased 13.9% ± 8.8%, whereas it decreased 10.5% ± 4.1% within SED. Furthermore, 24 weeks of exercise induced changes in the compliance measures between EX and SED. In addition, within EX muscle strength, exercise tolerance and lean tissue mass improved, whereas these remained stable within SED. Conclusion In conclusion, BDNF concentration of persons with RRMS was lower compared to HCs and increased after 24 weeks of exercise in persons with MS, compared to the non-exercise MS control group. [ABSTRACT FROM AUTHOR]

Background Intestinal dendritic cells ( DCs) maintain immune homeostasis, only initiating an active immune response against invading pathogens. However, little information is available on the reaction of mononuclear phagocytes ( MNP) to intestinal trematode infection, a reaction equally important in helminth-based therapies. The CD11c+ CX3 CR1+ F4/80− DCs in the ileal lamina propria ( LP) of the mouse were proven to migrate to the mesenteric lymph nodes ( MLNs). We analyzed all MNP subsets present in the mouse LP and MLNs, under steady-state conditions and during acute Schistosoma mansoni-induced inflammation. Furthermore, we studied the uptake of schistosomal antigens by MNP in vivo in the LP and MLNs. Methods Using a combination of immunohistochemistry and multiparametric flow cytometry, we investigated distributional changes of the MNP during acute intestinal schistosomiasis. Next, S. mansoni-derived products, i.e., S. mansoni soluble worm proteins (Sm SWP) and S. mansoni soluble egg antigens (Sm SEA) were intraperitoneally injected into CX3 CR1+/ GFP C57BL/6 mice and antigen uptake was analyzed using confocal microscopy. Key Results The CD11c+ CX3 CR1+ F4/80− DCs significantly increased during intestinal schistosomiasis in the LP and MLNs. Only CX3 CR1-expressing DC and MФ subsets, but not other LP DCs, are involved in both Sm SWP and Sm SEA antigen uptake and processing. Conclusions & inferences The significant upregulation of CD11c+ CX3 CR1+ F4/80− DCs during intestinal schistosomiasis and the restriction of phagocytosis of parasitic antigens to CX3 CR1-expresssing MNP indicate a crucial role for this immune cell niche in response to trematodiasis. These findings add insight into the functional specialization of LP immune cells and add to the understanding of cellular mechanisms behind helminth-based therapies. [ABSTRACT FROM AUTHOR]

Dendritic cells (DC) have important functions in T cell immunity and T cell tolerance. Previously, it was believed that T cell unresponsiveness induced by immature DC (iDC) is caused by the absence of inflammatory signals in steady-state in vivo conditions and by the low expression levels of costimulatory molecules on iDC. However, a growing body of evidence now indicates that iDC can also actively maintain peripheral T cell tolerance by the induction and/or stimulation of regulatory T cell populations. In this study, we investigated the in vitro T cell stimulatory capacity of iDC and mature DC (mDC) and found that both DC types induced a significant increase in the number of transforming growth factor (TGF)-β and interleukin (IL)-10 double-positive CD4+ T cells within 1 week of autologous DC/T cell co-cultures. In iDC/T cell cultures, where antigen-specific T cell priming was significantly reduced as compared to mDC/T cell cultures, we demonstrated that the tolerogenic effect of iDC was mediated by soluble TGF-β and IL-10 secreted by CD4+CD25-FOXP3- T cells. In addition, the suppressive capacity of CD4+ T cells conditioned by iDC was transferable to already primed antigen-specific CD8+ T cell cultures. In contrast, addition of CD4+ T cells conditioned by mDC to primed antigen-specific CD8+ T cells resulted in enhanced CD8+ T cell responses, notwithstanding the presence of TGF- β+/IL-10+ T cells in the transferred fraction. In summary, we hypothesize that DC have an active role in inducing immunosuppressive cytokine-secreting regulatory T cells.We show that iDC-conditioned CD4+ T cells are globally immunosuppressive, while mDC induce globally immunostimulatory CD4+ T cells. Furthermore, TGF- β+/IL-10+ T cells are expanded by DC independent of their maturation status, but their suppressive function is dependent on immaturity of DC. [ABSTRACT FROM AUTHOR]

Cashew soils of South Eastern Tanzania become acidified due to sulphur used for controlling powdery mildew disease (Oidium anacardii Noack). The buffering capacity of surface and subsurface horizons of 35 soil profiles of major cashew growing areas the Makonde plateau, its piedmont and inland plains was studied. The buffering capacity of surface and subsurface horizons was strongly correlated with clay contentand weakly with organic carbon content. In addition, it was only weakly correlated with total exchangeable bases and available P of the surface horizon, but strongly with soil pH, base saturation and cationexchange capacity of the clay fraction of the subsurface horizon. Highly weathered sandy soils, dominant on the Makonde plateau and common on the Piedmont, had the lowest buffering capacity. Soils from the inland plains had better buffering capacities as they are generally more clayey or are less weathered. The risk of severe acidification and of a decline in productivity of cashew and of food crops is higheston the Makonde plateau. Further development and dissemination of methods which can reduce the use of sulfur are required. [ABSTRACT FROM AUTHOR]

Cervarix™ is approved as a preventive vaccine against infection with the human papillomavirus (HPV) strains 16 and 18, which are causally related to the development of cervical cancer. We are the first to investigate in vitro the effects of this HPV vaccine on interleukin (IL)-15 dendritic cells (DC) as proxy of a naturally occurring subset of blood DC, and natural killer (NK) cells, two innate immune cell types that play an important role in antitumour immunity. Our results show that exposure of IL-15 DC to the HPV vaccine results in increased expression of phenotypic maturation markers, pro-inflammatory cytokine production and cytotoxic activity against HPV-positive tumour cells. These effects are mediated by the vaccine adjuvant, partly through Toll-like receptor 4 activation. Next, we demonstrate that vaccine-exposed IL-15 DC in turn induce phenotypic activation of NK cells, resulting in a synergistic cytotoxic action against HPV-infected tumour cells. Our study thus identifies a novel mode of action of the HPV vaccine in boosting innate immunity, including killing of HPV-infected cells by DC and NK cells., (© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Dendritic cells (DC) have important functions in T cell immunity and T cell tolerance. Previously, it was believed that T cell unresponsiveness induced by immature DC (iDC) is caused by the absence of inflammatory signals in steady-state in vivo conditions and by the low expression levels of costimulatory molecules on iDC. However, a growing body of evidence now indicates that iDC can also actively maintain peripheral T cell tolerance by the induction and/or stimulation of regulatory T cell populations. In this study, we investigated the in vitro T cell stimulatory capacity of iDC and mature DC (mDC) and found that both DC types induced a significant increase in the number of transforming growth factor (TGF)-beta and interleukin (IL)-10 double-positive CD4(+) T cells within 1 week of autologous DC/T cell co-cultures. In iDC/T cell cultures, where antigen-specific T cell priming was significantly reduced as compared to mDC/T cell cultures, we demonstrated that the tolerogenic effect of iDC was mediated by soluble TGF-beta and IL-10 secreted by CD4(+)CD25(-)FOXP3(-) T cells. In addition, the suppressive capacity of CD4(+) T cells conditioned by iDC was transferable to already primed antigen-specific CD8(+) T cell cultures. In contrast, addition of CD4(+) T cells conditioned by mDC to primed antigen-specific CD8(+) T cells resulted in enhanced CD8(+) T cell responses, notwithstanding the presence of TGF-beta(+)/IL-10(+) T cells in the transferred fraction. In summary, we hypothesize that DC have an active role in inducing immunosuppressive cytokine-secreting regulatory T cells. We show that iDC-conditioned CD4(+) T cells are globally immunosuppressive, while mDC induce globally immunostimulatory CD4(+) T cells. Furthermore, TGF-beta(+)/IL-10(+) T cells are expanded by DC independent of their maturation status, but their suppressive function is dependent on immaturity of DC.