Lactobacillus rhamnosus GG-supplemented formula expands butyrate-producing bacterial strains in food allergic infants.

Dietary intervention with extensively hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG (EHCF+LGG) accelerates tolerance acquisition in infants with cow's milk allergy (CMA). We examined whether this effect is attributable, at least in part, to an influence on the gut microbiota. Fecal samples from healthy controls (n=20) and from CMA infants (n=19) before and after treatment with EHCF with (n=12) and without (n=7) supplementation with LGG were compared by 16S rRNA-based operational taxonomic unit clustering and oligotyping. Differential feature selection and generalized linear model fitting revealed that the CMA infants have a diverse gut microbial community structure dominated by Lachnospiraceae (20.5±9.7%) and Ruminococcaceae (16.2±9.1%). Blautia, Roseburia and Coprococcus were significantly enriched following treatment with EHCF and LGG, but only one genus, Oscillospira, was significantly different between infants that became tolerant and those that remained allergic. However, most tolerant infants showed a significant increase in fecal butyrate levels, and those taxa that were significantly enriched in these samples, Blautia and Roseburia, exhibited specific strain-level demarcations between tolerant and allergic infants. Our data suggest that EHCF+LGG promotes tolerance in infants with CMA, in part, by influencing the strain-level bacterial community structure of the infant gut

To respond or not to respond - a personal perspective of intestinal tolerance

For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

Prion Seeding Activities of Mouse Scrapie Strains with Divergent PrPSc Protease Sensitivities and Amyloid Plaque Content Using RT-QuIC and eQuIC

Different transmissible spongiform encephalopathy (TSE)-associated forms of prion protein (e.g. PrPSc) can vary markedly in ultrastructure and biochemical characteristics, but each is propagated in the host. PrPSc propagation involves conversion from its normal isoform, PrPC, by a seeded or templated polymerization mechanism. Such a mechanism is also the basis of the RT-QuIC and eQuIC prion assays which use recombinant PrP (rPrPSen) as a substrate. These ultrasensitive detection assays have been developed for TSE prions of several host species and sample tissues, but not for murine models which are central to TSE pathogenesis research. Here we have adapted RT-QuIC and eQuIC to various murine prions and evaluated how seeding activity depends on glycophosphatidylinositol (GPI) anchoring and the abundance of amyloid plaques and protease-resistant PrPSc (PrPRes). Scrapie brain dilutions up to 10-8 and 10-13 were detected by RT-QuIC and eQuIC, respectively. Comparisons of scrapie-affected wild-type mice and transgenic mice expressing GPI anchorless PrP showed that, although similar concentrations of seeding activity accumulated in brain, the heavily amyloid-laden anchorless mouse tissue seeded more rapid reactions. Next we compared seeding activities in the brains of mice with similar infectivity titers, but widely divergent PrPRes levels. For this purpose we compared the 263K and 139A scrapie strains in transgenic mice expressing P101L PrPC. Although the brains of 263K-affected mice had no immunoblot-detectable PrPRes, RT-QuIC indicated that seeding activity was comparable to that associated with a high-PrPRes strain, 139A. Thus, in this comparison, RT-QuIC seeding activity correlated more closely with infectivity than with PrPRes levels. We also found that eQuIC, which incorporates a PrPSc immunoprecipitation step, detected seeding activity in plasma from wild-type and anchorless PrP transgenic mice inoculated with 22L, 79A and/or RML scrapie strains. Overall, we conclude that these new mouse-adapted prion seeding assays detect diverse types of PrPSc

Variation in Soil Respiration across Soil and Vegetation Types in an Alpine Valley.

BACKGROUND AND AIMS: Soils of mountain regions and their associated plant communities are highly diverse over short spatial scales due to the heterogeneity of geological substrates and highly dynamic geomorphic processes. The consequences of this heterogeneity for biogeochemical transfers, however, remain poorly documented. The objective of this study was to quantify the variability of soil-surface carbon dioxide efflux, known as soil respiration (Rs), across soil and vegetation types in an Alpine valley. To this aim, we measured Rs rates during the peak and late growing season (July-October) in 48 plots located in pastoral areas of a small valley of the Swiss Alps. FINDINGS: Four herbaceous vegetation types were identified, three corresponding to different stages of primary succession (Petasition paradoxi in pioneer conditions, Seslerion in more advanced stages and Poion alpinae replacing the climactic forests), as well as one (Rumicion alpinae) corresponding to eutrophic grasslands in intensively grazed areas. Soils were developed on calcareous alluvial and colluvial fan deposits and were classified into six types including three Fluvisols grades and three Cambisols grades. Plant and soil types had a high level of co-occurrence. The strongest predictor of Rs was soil temperature, yet we detected additional explanatory power of sampling month, showing that temporal variation was not entirely reducible to variations in temperature. Vegetation and soil types were also major determinants of Rs. During the warmest month (August), Rs rates varied by over a factor three between soil and vegetation types, ranging from 2.5 μmol m-2 s-1 in pioneer environments (Petasition on Very Young Fluvisols) to 8.5 μmol m-2 s-1 in differentiated soils supporting nitrophilous species (Rumicion on Calcaric Cambisols). CONCLUSIONS: Overall, this study provides quantitative estimates of spatial and temporal variability in Rs in the mountain environment, and demonstrates that estimations of soil carbon efflux at the watershed scale in complex geomorphic terrain have to account for soil and vegetation heterogeneity

Modulation of host responses by oral commensal bacteria.

Immunomodulatory commensal bacteria are proposed to be essential for maintaining healthy tissues, having multiple roles including priming immune responses to ensure rapid and efficient defences against pathogens. The default state of oral tissues, like the gut, is one of inflammation which may be balanced by regulatory mechanisms and the activities of anti-inflammatory resident bacteria that modulate Toll-like receptor (TLR) signalling or NF-κB activation, or influence the development and activities of immune cells. However, the widespread ability of normal resident organisms to suppress inflammation could impose an unsustainable burden on the immune system and compromise responses to pathogens. Immunosuppressive resident bacteria have been isolated from the mouth and, for example, may constitute 30% of the resident streptococci in plaque or on the tongue. Their roles in oral health and dysbiosis remain to be determined. A wide range of bacterial components and/or products can mediate immunomodulatory activity, raising the possibility of development of alternative strategies for therapy and health promotion using probiotics, prebiotics, or commensal-derived immunomodulatory molecules

Low-level regulatory T-cell activity is essential for functional type-2 effector immunity to expel gastrointestinal helminths

Helminth infection is frequently associated with the expansion of regulatory T cells (Tregs) and suppression of immune responses to bystander antigens. We show that infection of mice with the chronic gastrointestinal helminth Heligmosomoides polygyrus drives rapid polyclonal expansion of Foxp3(+)Helios(+)CD4(+) thymic (t)Tregs in the lamina propria and mesenteric lymph nodes while Foxp3(+)Helios(-)CD4(+) peripheral (p)Treg expand more slowly. Notably, in partially resistant BALB/c mice parasite survival positively correlates with Foxp3(+)Helios(+)CD4(+) tTreg numbers. Boosting of Foxp3(+)Helios(+)CD4(+) tTreg populations by administration of recombinant interleukin-2 (rIL-2):anti-IL-2 (IL-2C) complex increased worm persistence by diminishing type-2 responsiveness in vivo, including suppression of alternatively activated macrophage and granulomatous responses at the sites of infection. IL-2C also increased innate lymphoid cell (ILC) numbers, indicating that Treg functions dominate over ILC effects in this setting. Surprisingly, complete removal of Tregs in transgenic Foxp3-DTR mice also resulted in increased worm burdens, with "immunological chaos" evident in high levels of the pro-inflammatory cytokines IL-6 and interferon-γ. In contrast, worm clearance could be induced by anti-CD25 antibody-mediated partial depletion of early Treg, alongside increased T helper type 2 responses and without incurring pathology. These findings highlight the overarching importance of the early Treg response to infection and the non-linear association between inflammation and the prevailing Treg frequency

On the Bitrate Adaptation of Shared Media Experience Services

In Shared Media Experience Services (SMESs), a group of people is interested in streaming consumption in a synchronised way, like in the case of cloud gaming, live streaming, and interactive social applications. However, group synchronisation comes at the expense of other Quality of Experience (QoE) factors due to both the dynamic and diverse network conditions that each group member experiences. Someone might wonder if there is a way to keep a group synchronised while maintaining the highest possible QoE for each one of its members. In this work, at first we create a Quality Assessment Framework capable of evaluating different SMESs improvement approaches with respect to traditional metrics like media bitrate quality, playback disruption, and end user desynchronisation. Secondly, we focus on the bitrate adaptation for improving the QoE of SMESs, as an incrementally deployable end user triggered approach, and we formulate the problem in the context of Adaptive Real Time Dynamic Programming (ARTDP). Finally, we develop and apply a simple QoE aware bitrate adaptation mechanism that we compare against youtube live-streaming traces to find that it improves the youtube performance by more than 30%

More stories on Th17 cells

For more than two decades, immunologists have been using the so-called Th1/Th2 paradigm to explain most of the phenomena related to adaptive immunity. the Th1/Th2 paradigm implied the existence of two different, mutually regulated, CD4(+) T helper subsets: Th1 cells, driving cell-mediated immune responses involved in tissue damage and fighting infection against intracellular parasites; and Th2 cells that mediate IgE production and are particularly involved in eosinophilic inflammation, allergy and clearance of helminthic infections. A third member of the T helper set, IL-17-producing CD4(+) T cells, now called Th17 cells, was recently described as a distinct lineage that does not share developmental pathways with either Th1 or Th2 cells. the Th17 subset has been linked to autoimmune disorders, being able to produce IL-17, IL-17F and IL-21 among other inflammatory cytokines. Interestingly, it has been reported that there is not only a cross-regulation among Th1, Th2 and Th17 effector cells but there is also a dichotomy in the generation of Th17 and T regulatory cells. Therefore, Treg and Th17 effector cells arise in a mutually exclusive fashion, depending on whether they are activated in the presence of TGF-beta or TGF-beta plus inflammatory cytokines such as IL-6. This review will address the discovery of the Th17 cells, and recent progress on their development and regulation.Crohn's and Colitis Foundation of AmericaNIHLa Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USAUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, BrazilNIH: RO1 AI050265-06Web of Scienc

Conformational Properties of Prion Strains Can Be Transmitted to Recombinant Prion Protein Fibrils in Real-Time Quaking-Induced Conversion

The phenomenon of prion strains with distinct biological characteristics has been hypothesized to be involved in the structural diversity of abnormal prion protein (PrPSc). However, the molecular basis of the transmission of strain properties remains poorly understood. Real-time quaking-induced conversion (RT-QUIC) is a cell-free system that uses Escherichia coli-derived recombinant PrP (rPrP) for the sensitive detection of PrPSc. To investigate whether the properties of various prion strains can be transmitted to amyloid fibrils consisting of rPrP (rPrP fibrils) using RT-QUIC, we examined the secondary structure, conformational stability, and infectivity of rPrP fibrils seeded with PrPSc derived from either the Chandler or the 22L strain. In the first round of the reaction, there were differences in the secondary structures, especially in bands attributed to β-sheets, as determined by infrared spectroscopy, and conformational stability between Chandler-seeded (1st-rPrP-fibCh) and 22L-seeded (1st-rPrP- fib22L) rPrP fibrils. Of note, specific identifying characteristics of the two rPrP fibril types seen in the β-sheets resembled those of the original PrPSc. Furthermore, the conformational stability of 1st-rPrP-fibCh was significantly higher than that of 1strPrP- fib22L, as with Chandler and 22L PrPSc. The survival periods of mice inoculated with 1st-rPrP-fibCh or 1st-rPrP-fib22L were significantly shorter than those of mice inoculated with mixtures from the mock 1st-round RT-QUIC procedure. In contrast, these biochemical characteristics were no longer evident in subsequent rounds, suggesting that nonspecific uninfected rPrP fibrils became predominant probably because of their high growth rate. Together, these findings show that at least some strainspecific conformational properties can be transmitted to rPrP fibrils and unknown cofactors or environmental conditions may be required for further conservation

High diagnostic value of second generation CSF RT-QuIC across the wide spectrum of CJD prions

Abstract An early and accurate in vivo diagnosis of rapidly progressive dementia remains challenging, despite its critical importance for the outcome of treatable forms, and the formulation of prognosis. Real-Time Quaking-Induced Conversion (RT-QuIC) is an in vitro assay that, for the first time, specifically discriminates patients with prion disease. Here, using cerebrospinal fluid (CSF) samples from 239 patients with definite or probable prion disease and 100 patients with a definite alternative diagnosis, we compared the performance of the first (PQ-CSF) and second generation (IQ-CSF) RT-QuIC assays, and investigated the diagnostic value of IQ-CSF across the broad spectrum of human prions. Our results confirm the high sensitivity of IQ-CSF for detecting human prions with a sub-optimal sensitivity for the sporadic CJD subtypes MM2C and MM2T, and a low sensitivity limited to variant CJD, Gerstmann-Sträussler-Scheinker syndrome and fatal familial insomnia. While we found no difference in specificity between PQ-CSF and IQ-CSF, the latter showed a significant improvement in sensitivity, allowing prion detection in about 80% of PQ-CSF negative CJD samples. Our results strongly support the implementation of IQ-CSF in clinical practice. By rapidly confirming or excluding CJD with high accuracy the assay is expected to improve the outcome for patients and their enrollment in therapeutic trials