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Scooped by
Gilbert C FAURE
October 12, 2017 5:03 AM
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Mucosal immunity to reinfection with a highly virulent virus requires the accumulation and persistence of memory CD8 T cells at the site of primary infection. These cells may derive from memory precursor effector cells (MPECs), which are distinct from short-lived effector cells that provide acute protection but are often destined to die. Using respiratory virus infection, we show that herpes virus entry mediator (HVEM; TNFRSF14), a member of the TNF receptor superfamily, provides key signals for MPEC persistence. HVEM-deficient CD8 T cells expanded normally but were skewed away from MPECs with resultant poor development of circulating and lung-resident memory cells. HVEM was selectively expressed on MPECs whereas MPECs deficient in HVEM failed to survive in adoptive transfer recipients. As a consequence, HVEM-deficient recipients failed to afford protection against respiratory reinfection with influenza virus. HVEM therefore represents a critical signal for MPECs and development of protective mucosal CD8 T cell memory. This article is featured in In This Issue , p.[2609][1] [1]: /lookup/volpage/199/2609
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Scooped by
Gilbert C FAURE
October 12, 2017 1:59 AM
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Scooped by
Gilbert C FAURE
October 10, 2017 8:32 AM
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LETTER TO THE EDITOR Recurrent urinary tract infections and low secretory IgA following CD19-directed CAR T-cell therapy for relapsed acute lymphoblastic leukemia Bettina Isaac McGraw1, Colleen Sweeney2 andSüreyya Savaşan1,2,* Version of Record online: 2 AUG 2017 DOI: 10.1002/pbc.26739 © 2017...
Via Krishan Maggon
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Scooped by
Gilbert C FAURE
October 9, 2017 8:47 AM
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Scooped by
Gilbert C FAURE
October 9, 2017 3:39 AM
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Zika virus RNA is frequently detected in the semen of men after Zika virus infection. To learn more about persistence of viruses in genital fluids, we searched PubMed for relevant articles. We found evidence that 27 viruses, across a broad range of virus families, can be found in human semen.
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Scooped by
Gilbert C FAURE
October 5, 2017 7:53 AM
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Scooped by
Gilbert C FAURE
October 5, 2017 7:53 AM
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Background: The mechanism underlying transient increases in immunoglobulin (Ig) A concentrations in the cecal contents of rats fed fructo-oligosaccharide (FOS) is unclear. Objective: This study was designed to test whether increased IgA concentrations represent one aspect of the inflammatory response to increased permeability induced by FOS in the cecum. Methods: Seven-week-old male Wistar rats were fed a fiber-free semipurified diet (FFP) with or without supplemental FOS (60 g/kg diet) for 9 or 58 d [experiment (expt.) 1], 7 d (expt. 2), or 7 or 56 d (expt. 3). In addition to measuring IgA concentrations in cecal content, we assessed gut permeability, inflammatory responses (expt. 1), the number of IgA plasma cells in the cecal lamina propria, polymeric Ig receptor (pIgR) expression in the cecal mucosa (expt. 2), and the condition of the cecal mucus layer (expt. 3). Results: The cecal IgA concentration in the FOS-fed rats was 15-fold higher than that of the rats fed FFP for 9 d (P < 0.05). Gut permeability estimated by urinary chromium-EDTA excretion, bacterial translocation to mesenteric lymph nodes, myeloperoxidase activity, and expression of inflammatory cytokine genes in the cecal mucosa was greater in the FOS-fed rats than in the rats fed FFP for 9 d. These effects were not observed in the rats fed FOS for 58 d (expt. 1). Accompanying the higher cecal IgA concentration, pIgR protein and the number of IgA plasma cells in the cecal mucosa were higher in the FOS-fed rats than in the rats fed FFP for 7 d (expt. 2). Destruction of the mucus layer on the epithelial surface, as evidenced by Alcian blue staining in the cecal sections, was evident in the rats fed FOS for 7 d, but the mucus layer appeared normal in the rats fed FOS for 56 d (expt. 3). Conclusions: These findings suggest that transient increases in cecal IgA concentrations induced by FOS in rats are associated with mucosal inflammation in response to increased gut permeability; these are presumably evoked by disruption of the cecal mucus barrier. The observed responses could contribute to the maturation of the gut immune system.
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Scooped by
Gilbert C FAURE
October 5, 2017 7:52 AM
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Rescooped by
Gilbert C FAURE
from Luxembourg (Europe)
October 5, 2017 3:56 AM
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The role of materials and hygiene in the transmission of bacteria in public places, a research project on the prevention of bacterial contamination that European School student Camilla Hurst has performed over the last three years in collaboration with both her school and the Luxembourg Institute of Science and Technology (LIST). This project won a special prize from the Swiss nutritional products firm DSM, who have invited Camilla to visit one of their research centres in Switzerland. Learn more / En savoir plus / Mehr erfahren: http://www.scoop.it/t/luxembourg-europe/?&tag=STEM
Via Gust MEES
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Scooped by
Gilbert C FAURE
October 3, 2017 2:09 PM
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Large quantities of immunoglobulin A (IgA) are constitutively secreted by intestinal plasma cells to coat and contain the commensal microbiota, yet the specificity of these antibodies remains elusive. Here, we profiled the reactivities of single murine IgA plasma cells by cloning and characterizing large numbers of monoclonal antibodies. IgAs were not specific to individual bacterial taxa but rather polyreactive, with broad reactivity to a diverse but defined subset of microbiota. These antibodies arose at low frequencies among naïve B cells, and were selected into the IgA repertoire upon recirculation in Peyer’s patches. This selection process occurred independent of microbiota or dietary antigens. Furthermore, while some IgAs acquired somatic mutations, these did not substantially influence their reactivity. These findings reveal an endogenous mechanism driving homeostatic production of polyreactive IgAs with innate specificity to microbiota.
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Rescooped by
Gilbert C FAURE
from MRC research in the news
October 2, 2017 9:42 AM
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Fresh insights into how cystic fibrosis affects immune cells could pave the way for new treatments for the condition, Scots researchers believe.
Via MRC press office
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Scooped by
Gilbert C FAURE
October 1, 2017 3:33 AM
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Evidence has shown that dysbiosis of the urinary microbiota existed in female type 2 diabetes mellitus (T2DM) patients. Perturbations of intestinal microbiota are linked to proinflammatory chemokine interleukin-8 (IL-8); however, the correlations between urinary microbiota and IL-8 are not well studied. Here, we investigated the associations between the altered urinary microbiota and urinary IL-8 in female T2DM patients. A modified four-tube midstream urine technique was used to collect urine specimens from 70 female T2DM patients and 70 matched healthy controls (HCs). Bacterial genomic DNA from urine specimens was isolated using magnetic beads and the urinary microbiota was assessed using Illumina MiSeq platform targeting on the 16S rRNA gene V3-V4 region. Urinary IL-8 was determined by enzyme linked immunosorbent assay. Subsequently, the T2DM patients were separated into urine IL-8 detectable (WIL8) and undetectable (NIL8) groups, and the composition of urinary microbiota between the two groups was compared. Meanwhile, the levels of IL-8 between the “≥HCs” group (those specific bacterial genera were more than or equal to the HCs) and the “
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Suggested by
Société Francaise d'Immunologie
October 12, 2017 2:08 AM
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Scooped by
Gilbert C FAURE
October 10, 2017 1:41 PM
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Type 1 diabetes has a multifactorial etiology. Lehuen and colleagues demonstrate that MAIT cells serve both positive roles and negative roles in type 1 diabetes by maintaining gut integrity and limiting pancreatic inflammation but also directly destroying [beta]-cells.
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Scooped by
Gilbert C FAURE
October 10, 2017 8:29 AM
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Objective Anti-NKG2D (NNC0142-0002) is an antagonising human immunoglobulin G4 monoclonal antibody that binds to natural killer group 2 member D (NKG2D) receptors, which are expressed by T cells and innate lymphoid cells, and may be linked to mucosal damage in Crohn's disease (CD). Design Seventy-eight patients (aged ≥18 and ≤75 years) with CD for ≥3 months, Crohn's Disease Activity Index (CDAI) ≥220 and ≤450 and either C-reactive protein ≥10 mg/L or endoscopic evidence of inflammation, were randomised 1:1 to a single subcutaneous (SC) dose of 2 mg/kg anti-NKG2D or placebo. Primary endpoint was change in CDAI (ΔCDAI) from baseline to week 4. Prespecified significance level was 10% for CDAI endpoints. A futility analysis was instituted due to slow recruitment. Results Primary endpoint was not significantly different between anti-NKG2D and placebo (week 4 ΔCDAI=–16); however, there was a significant difference by week 12 (ΔCDAI=–55; p≤0.10). Significant improvements were noted in the non-failure to biologics subgroup (treated with anti-NKG2D (n=28)) from week 1 onward. Greater effects of anti-NKG2D were also observed in patients with baseline CDAI ≥330. Frequencies of adverse events (AEs) were comparable between anti-NKG2D and placebo. Most AEs were mild (49%) or moderate (43%). No antidrug antibodies were observed. Conclusions A single SC dose of 2 mg/kg anti-NKG2D did not reduce disease activity at week 4 versus placebo, but the difference was significant at week 12, and effects were evident in key subgroups. These data support further development of anti-NKG2D in IBD. Trial registration number NCT01203631.
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Scooped by
Gilbert C FAURE
October 9, 2017 8:50 AM
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Development and regulation of single- and multi-species Candida albicans biofilms
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Scooped by
Gilbert C FAURE
October 9, 2017 8:44 AM
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CD4+CD8αα+ double-positive intraepithelial lymphocytes (DP IELs) are a recently discovered class of intestinal T cells believed to take part in a variety of immune responses, including oral tolerance. These cells are absent in germ-free mice, but the mechanisms driving their development are unclear. Cervantes-Barragan et al. found that a particular species of probiotic bacteria, Lactobacillus reuteri , induces DP IELs. This does not occur by stimulating the immune system directly. Instead, L. reuteri generates a specific derivative of dietary tryptophan that promotes differentiation of DP IEL precursors. These findings underscore the delicate interplay between benign bacteria, diet, and gut health. Science , this issue p. [806][1] [1]: /lookup/doi/10.1126/science.aah5825
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Scooped by
Gilbert C FAURE
October 7, 2017 1:44 PM
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Infection or inflammation of the skin recruits effector CD8+ T cells that enter the epidermis and form populations of long-lived tissue-resident memory T (TRM) cells. These skin TRM cells migrate within the constrained epidermal environment by extending multiple dynamic dendritic projections and squeezing between keratinocytes to survey the tissue for pathogens. In this study, we examined the signals required for this distinctive mode of T cell migration by inhibiting key cytoskeletal components and performing intravital two-photon microscopy to visualize TRM cell behavior. We found that TRM cell motility and dendrite formation required an intact actomyosin cytoskeleton and the Rho-associated coiled-coil containing kinases. We also identified an essential role for microtubules for maintaining skin TRM cell shape and cellular integrity. We reveal a role for pertussis toxin–sensitive signaling for TRM cell dendritic morphology and migration that is independent of CXCR3 or CXCR6, or the skin-selective chemokine receptors CCR10 and CCR8. However, we found that CXCR6 and CCR10 expression by CD8+ T cells was required for the optimal formation of memory T cell populations, in particular TRM cell populations in the skin.
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Scooped by
Gilbert C FAURE
October 5, 2017 7:53 AM
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The fungal pathogen, Cryptococcus neoformans, causes devastating levels of morbidity and mortality. Infections with this fungus tend to be predominantly in immunocompromised individuals, such as those with HIV. Infections initiate with inhalation of cryptococcal cells and entry of the pathogen into the lungs. The bronchial epithelial cells of the upper airway and the alveolar epithelial cells of the lower airway are likely to be the first host cells that Cryptococcus engage with. Thus the interaction of cryptococci and the respiratory epithelia will be the focus of this review. C. neoformans has been shown to adhere to respiratory epithelial cells, although if the role of the capsule is in aiding or hindering this adhesion is debatable. The epithelia are also able to react to cryptococci with the release of cytokines and chemokines to start the immune response to this invading pathogen. The activity of surfactant components that line this mucosal barrier towards Cryptococcus and the metabolic and transcriptional reaction of cryptococci when encountering epithelial cells will also be discussed.
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Scooped by
Gilbert C FAURE
October 5, 2017 7:52 AM
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Adult‐onset IgA vasculitis (IgAV, formerly Henoch‐Schönlein purpura) is a rare systemic vasculitis characterised by IgA1‐dominant deposits. The treatment of adult‐onset IgAV is controversial and i
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Scooped by
Gilbert C FAURE
October 5, 2017 7:51 AM
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Benefits of green tea were already known; new UCLA study shows that polyphenols in both varieties alter gut bacteria
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Scooped by
Gilbert C FAURE
October 4, 2017 8:18 AM
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Composed of trillions of individual microbes, the human gut microbiota has adapted to the uniquely diverse environments found in the human intestine. Quickly responding to the variances in the ingested food, the microbiota interacts with the host via reciprocal biochemical signaling to coordinate the exchange of nutrients and proper immune function. Host and microbiota function as a unit which guards its balance against invasion by potential pathogens and which undergoes natural selection. Disturbance of the microbiota composition, or dysbiosis, is often associated with human disease, indicating that, while there seems to be no unique optimal composition of the gut microbiota, a balanced community is crucial for human health. Emerging knowledge of the ecology of the microbiota-host synergy will have an impact on how we implement antibiotic treatment in therapeutics and prophylaxis and how we will consider alternative strategies of global remodeling of the microbiota such as faecal transplants. Here we examine the microbiota-human host relationship from the perspective of the microbial community dynamics.
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Scooped by
Gilbert C FAURE
October 2, 2017 11:35 AM
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Scooped by
Gilbert C FAURE
October 2, 2017 8:46 AM
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Targeting microbial biofilms: current and prospective therapeutic strategies
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