18 research outputs found

    Regulation of type 1 diabetes development and B-cell activation in nonobese diabetic mice by early life exposure to a diabetogenic environment

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    Microbes, including viruses, influence type 1 diabetes (T1D) development, but many such influences remain undefined. Previous work on underlying immune mechanisms has focussed on cytokines and T cells. Here, we compared two nonobese diabetic (NOD) mouse colonies, NODlow and NODhigh, differing markedly in their cumulative T1D incidence (22% vs. 90% by 30 weeks in females). NODhigh mice harbored more complex intestinal microbiota, including several pathobionts; both colonies harbored segmented filamentous bacteria (SFB), thought to suppress T1D. Young NODhigh females had increased B-cell activation in their mesenteric lymph nodes. These phenotypes were transmissible. Co-housing of NODlow with NODhigh mice after weaning did not change T1D development, but T1D incidence was increased in female offspring of co-housed NODlow mice, which were exposed to the NODhigh environment both before and after weaning. These offspring also acquired microbiota and B-cell activation approaching those of NODhigh mice. In NODlow females, the low rate of T1D was unaffected by cyclophosphamide but increased by PD-L1 blockade. Thus, environmental exposures that are innocuous later in life may promote T1D progression if acquired early during immune development, possibly by altering B-cell activation and/or PD-L1 function. Moreover, T1D suppression in NOD mice by SFB may depend on the presence of other microbial influences. The complexity of microbial immune regulation revealed in this murine model may also be relevant to the environmental regulation of human T1D

    Impact of early life exposures to geohelminth infections on the development of vaccine immunity, allergic sensitization, and allergic inflammatory diseases in children living in tropical Ecuador: the ECUAVIDA birth cohort study.

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    Background Geohelminth infections are highly prevalent infectious diseases of childhood in many regions of the Tropics, and are associated with significant morbidity especially among pre-school and school-age children. There is growing concern that geohelminth infections, particularly exposures occurring during early life in utero through maternal infections or during infancy, may affect vaccine immunogenicity in populations among whom these infections are endemic. Further, the low prevalence of allergic disease in the rural Tropics has been attributed to the immune modulatory effects of these infections and there is concern that widespread use of anthelmintic treatment in high-risk groups may be associated with an increase in the prevalence of allergic diseases. Because the most widely used vaccines are administered during the first year of life and the antecedents of allergic disease are considered to occur in early childhood, the present study has been designed to investigate the impact of early exposures to geohelminths on the development of protective immunity to vaccines, allergic sensitization, and allergic disease. Methods/Design A cohort of 2,403 neonates followed up to 8 years of age. Primary exposures are infections with geohelminth parasites during the last trimester of pregnancy and the first 2 years of life. Primary study outcomes are the development of protective immunity to common childhood vaccines (i.e. rotavirus, Haemophilus influenzae type B, Hepatitis B, tetanus toxoid, and oral poliovirus type 3) during the first 5 years of life, the development of eczema by 3 years of age, the development of allergen skin test reactivity at 5 years of age, and the development of asthma at 5 and 8 years of age. Potential immunological mechanisms by which geohelminth infections may affect the study outcomes will be investigated also. Discussion The study will provide information on the potential effects of early exposures to geohelminths (during pregnancy and the first 2 years of life) on the development of vaccine immunity and allergy. The data will inform an ongoing debate of potential effects of geohelminths on child health and will contribute to policy decisions on new interventions designed to improve vaccine immunogenicity and protect against the development of allergic diseases

    Experimental evidence for sustained carbon sequestration in fire-managed, peat moorlands.

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    Peat moorlands are important habitats in the boreal region, where they store approximately 30% of the global soil carbon (C). Prescribed burning on peat is a very contentious management strategy, widely linked with loss of carbon. Here, we quantify the effects of prescribed burning for lightly managed boreal moorlands and show that the impacts on peat and C accumulation rates are not as bad as is widely thought. We used stratigraphical techniques within a unique replicated ecological experiment with known burn frequencies to quantify peat and C accumulation rates (0, 1, 3 and 6 managed burns since around 1923). Accumulation rates were typical of moorlands elsewhere, and were reduced significantly only in the 6-burn treatment. However, impacts intensified gradually with burn frequency; each additional burn reduced the accumulation rates by 4.9 g m−2 yr−1 (peat) and 1.9 g C cm−2 yr−1, but did not prevent accumulation. Species diversity and the abundance of peat-forming species also increased with burn frequency. Our data challenge widely held perceptions that a move to 0 burning is essential for peat growth, and show that appropriate prescribed burning can both mitigate wildfire risk in a warmer world and produce relatively fast peat growth and sustained C sequestration

    Changes in bacterial and archaeal community assemblages along an ombrotrophic peat bog profile

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    Peatlands are archives of extreme importance for the assessment of past ecological, environmental and climatic changes. The importance as natural archives is even greater in the case of ombrotrophic peat bogs, where the only inputs are atmospheric in origin. Here we integrated previously published physical and chemical results regarding the solid and liquid phase of peat with a biomolecular microbiological approach to assess the relationships between chemistry and microbial biodiversity along a Swiss bog profile corresponding to approximately 2,000 years of peat formation. The structure of bacterial and archaeal communities was assessed through a polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) approach followed by sequencing of PCR-DGGE bands of interest. Both chemical and microbiological data showed a differentiation of properties along the peat profile, with three major zones identified. Both bacterial and archaeal profiles clustered according to the depth (i.e., age) of samples. Among bacteria, Acidobacteria were recovered primarily in the first layers of the profile, whereas methanogenic archaea were more commonly recovered in the deepest part of the core, corresponding to the occurring anoxic conditions. Finally, a number of sequences had low homologies with known species, especially in bacteria: this points to an almost unknown microbial community adapted to the extreme conditions of peat bogs, which are acidic, rich in dissolved organic C, and predominantly anoxic. \ua9 2014 Springer-Verlag Berlin Heidelberg

    The evolution of nitric oxide signalling in vertebrate blood vessels

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