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Scooped by
Gilbert C FAURE
July 12, 2017 4:18 AM
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Scooped by
Gilbert C FAURE
July 11, 2017 3:32 PM
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Little is known about the relative importance of monocyte and tissue-resident macrophages in the development of lung fibrosis. We show that specific genetic deletion of monocyte-derived alveolar macrophages after their recruitment to the lung ameliorated lung fibrosis, whereas tissue-resident alveolar macrophages did not contribute to fibrosis. Using transcriptomic profiling of flow-sorted cells, we found that monocyte to alveolar macrophage differentiation unfolds continuously over the course of fibrosis and its resolution. During the fibrotic phase, monocyte-derived alveolar macrophages differ significantly from tissue-resident alveolar macrophages in their expression of profibrotic genes. A population of monocyte-derived alveolar macrophages persisted in the lung for one year after the resolution of fibrosis, where they became increasingly similar to tissue-resident alveolar macrophages. Human homologues of profibrotic genes expressed by mouse monocyte-derived alveolar macrophages during fibrosis were up-regulated in human alveolar macrophages from fibrotic compared with normal lungs. Our findings suggest that selectively targeting alveolar macrophage differentiation within the lung may ameliorate fibrosis without the adverse consequences associated with global monocyte or tissue-resident alveolar macrophage depletion.
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Scooped by
Gilbert C FAURE
July 9, 2017 3:20 AM
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bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution
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Suggested by
LIGHTING
July 7, 2017 1:56 PM
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It turns out your skin is crawling with single-celled microorganisms—and they're not just bacteria. A study by the Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) and the Medical University o
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Rescooped by
Gilbert C FAURE
from AUTOIMMUNITY
July 6, 2017 9:37 AM
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Recent evidences suggest that human gut microbiota with major component as bacteria can induce immunity. It is also known that gut lining depletes with ageing and that there is increased risk of autoimmune and inflammatory disorders with ageing. It is therefore likely that both may be correlated as depletion of gut lining exposes the gut bacterial antigens to host immune mechanisms, which may induce immunity to certain bacterial proteins, but at the same time such immunity may also be auto-immunogenic to host. This autoimmunity may make a protein molecule nonfunctional and thereby may be involved in late onset metabolic, autoimmune and inflammatory disorders such as, Diabetes, Rheumatoid Arthritis, Hyperlipidemias and Cancer. In this in-silico study we found a large number of peptides identical between human and gut bacteria which were binding to HLA-II alleles, and hence, likely to be auto-immunogenic. Further we observed that such autoimmune candidates were enriched in bacterial species belonging to Firmicutes and Proteobacteria phyla, which lead us to conclude that these phyla may have higher disease impact in genetically predisposed individuals. Functional annotation of human proteins homologous to candidate gut-bacterial peptides showed significant enrichment in metabolic processes and pathways. Cognitive trait, Ageing, Alzheimer, Type 2 diabetes, Chronic Kidney Failure (CKF), Chronic Obstructive Pulmonary Disease (COPD) and various Cancers were the major diseases represented in the dataset. This dataset provides us with gut bacterial autoimmune candidates which can be studied for their clinical significance in late onset diseases.
Via Krishan Maggon , Gilbert C FAURE
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Scooped by
Gilbert C FAURE
July 5, 2017 10:34 AM
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Human respiratory syncytial virus (hRSV) is the leading cause of severe lower respiratory tract infections in children. The development of novel prophylactic and therapeutic antiviral drugs against hRSV is imperative to control the burden of disease in the susceptible population. In this study, we examined the effects of inducing the activity of the host enzyme heme oxygenase-1 (HO-1) on hRSV replication and pathogenesis on lung inflammation induced by this virus. Our results show that after hRSV infection, HO-1 induction with metalloporphyrin cobalt protoporphyrin IX significantly reduces the loss of body weight due to hRSV-induced disease. Further, HO-1 induction also decreased viral replication and lung inflammation, as evidenced by a reduced neutrophil infiltration into the airways, with diminished cytokine and chemokine production and reduced T cell function. Concomitantly, upon cobalt protoporphyrin IX treatment, there is a significant upregulation in the production of IFN-α/β mRNAs in the lungs. Furthermore, similar antiviral and protective effects occur by inducing the expression of human HO-1 in MHC class II+ cells in transgenic mice. Finally, in vitro data suggest that HO-1 induction can modulate the susceptibility of cells, especially the airway epithelial cells, to hRSV infection.
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Scooped by
Gilbert C FAURE
July 3, 2017 1:41 PM
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The mammalian gut is colonized by trillions of microorganisms collectively called
the microbiome. It is increasingly clear that this microbiome has a critical role
of in many aspects of health including metabolism and immunity. While environmental
factors such as diet and medications have been shown to influence the microbiome composition,
the role of host genetics has only recently emerged in human studies and animal models.
In this review, we summarize the current state of microbiome research with an emphasis
on the effect of host genetics on the gut microbiome composition.
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Scooped by
Gilbert C FAURE
July 3, 2017 6:44 AM
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The European Rhinology Research Forum will be held in Brussels, Belgium, on 9-10 November 2017, under the auspicies of EUFOREA and ERS.
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Scooped by
Gilbert C FAURE
July 3, 2017 1:59 AM
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After its initial discoveries in the 1980s and 1990s, neuro-immunology is experiencing
a rebirth in the scientific literature. As knowledge of the gastrointestinal tract
expands, including its neuronal, immunological, and microbial constituents, in this
review, Yoo and Mazmanian provide new perspectives and hypotheses regarding mucosal
neuro-immunology.
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Scooped by
Gilbert C FAURE
July 1, 2017 5:03 AM
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Author summary Superantigens (SAgs) are toxins produced by Staphylococcus aureus and Streptococcus pyogenes, microbes that are responsible for a multitude of infectious diseases and conditions. Once released, SAgs activate many immune cells, resulting in a massive inflammatory response that is often followed by a state of immunosuppression, a state that favors opportunistic infections. Using primary human cells as well as wild-type and genetically altered mice, we have now identified a subset of unconventional, innate-like T lymphocytes, called mucosa-associated invariant T (MAIT) cells, as one of the most powerful and quick-acting sources of inflammatory mediators in the aftermath of systemic exposure to SAgs. We also demonstrate that robust activation of MAIT cells by SAgs quickly leads to their exhaustion, and this exhaustion interferes with their ability to participate in antimicrobial host defense and contributes to the immunosuppressive state. Our findings thus define a pathogenic role for MAIT cells during Gram-positive bacterial infections and also uncover a novel mechanism of SAg-mediated immunosuppression. Accordingly, we propose that MAIT cells can be targeted for efficacious treatment of SAg-mediated illnesses.
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Scooped by
Gilbert C FAURE
July 1, 2017 5:01 AM
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IgA nephropathy (IgAN), the most common GN worldwide, is characterized by circulating galactose-deficient IgA (gd-IgA) that forms immune complexes. The immune complexes are deposited in the glomerular mesangium, leading to inflammation and loss of renal function, but the complete pathophysiology of the disease is not understood. Using an integrated global transcriptomic and proteomic profiling approach, we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsy specimens from patients with IgAN (n=19) and controls (n=22). Using curated glomerular cell type–specific genes from the published literature, we found differential expression of a much higher percentage of mesangial cell–positive standard genes than podocyte-positive standard genes in IgAN. Principal coordinate analysis of expression data revealed clear separation of patient and control samples on the basis of mesangial but not podocyte cell–positive standard genes. Additionally, patient clinical parameters (serum creatinine values and eGFRs) significantly correlated with Z scores derived from the expression profile of mesangial cell–positive standard genes. Among patients grouped according to Oxford MEST score, patients with segmental glomerulosclerosis had a significantly higher mesangial cell–positive standard gene Z score than patients without segmental glomerulosclerosis. By investigating mesangial cell proteomics and glomerular transcriptomics, we identified 22 common pathways induced in mesangial cells by gd-IgA, most of which mediate inflammation. The genes, proteins, and corresponding pathways identified provide novel insights into the pathophysiologic mechanisms leading to IgAN.
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Scooped by
Gilbert C FAURE
July 1, 2017 4:56 AM
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AIDS. 2017 Jul 17;31(11):1529-1534. doi: 10.1097/QAD.0000000000001515.
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Scooped by
Gilbert C FAURE
June 29, 2017 12:59 PM
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Suggested by
Société Francaise d'Immunologie
July 12, 2017 3:34 AM
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Discover the role played by mucosal immunology in immune defense. Overview of the structure and regulation of mucosal homeostasis and how this relates to disease and potential immunotherapy.
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Scooped by
Gilbert C FAURE
July 11, 2017 8:50 AM
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This literature review assesses the current knowledge about the immunological aspects of the vermiform appendix in health and disease. An essential part of its immunological function is th
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Scooped by
Gilbert C FAURE
July 8, 2017 1:51 AM
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Type I and type III interferons (IFNs) are crucial components of the first line antiviral host response. While specific receptors for both IFN types exist, intracellular signaling shares the same Jak-STAT pathway. Due to its receptor expression IFN-λ responsiveness is restricted mainly to epithelial cells. Here we display IFN-stimulated gene induction at the single cell level to comparatively analyze the activities of both IFN types in intestinal epithelial cells and mini-gut organoids. Initially, we noticed that the response to both types of IFN at low concentrations is based on a single cell decision making determining the total cell intrinsic antiviral activity. We identified HDAC activity as a crucial restriction factor controlling the cell frequency of ISG induction upon IFN-λ but not IFN-β stimulation. Consistently, HDAC blockade confers antiviral activity to an elsewise non-responding subpopulation. Second, in contrast to the type I IFN system, polarization of intestinal epithelial cells strongly enhances their ability to respond to IFN-λ signaling and raises the kinetics of gene induction. Finally, we show that ISG induction in mini-gut organoids by low amounts of IFN is characterized by a scattered heterogeneous responsiveness of the epithelial cells and HDAC activity fine tunes exclusively IFN-λ activity. This study provides a comprehensive description of the differential response to type I and type III IFNs and demonstrates that cell polarization in gut epithelial cells specifically increases IFN-λ activity.
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Scooped by
Gilbert C FAURE
July 7, 2017 4:01 AM
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One writer tried an at-home microbiome test to evaluate her gut health—here's what she learned.
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Scooped by
Gilbert C FAURE
July 5, 2017 2:50 PM
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Scooped by
Gilbert C FAURE
July 4, 2017 11:43 AM
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Strong T cell receptor (TCR) signaling largely induces cell death during thymocyte development, whereas weak TCR signals induce positive selection. However, some T cell lineages require strong TCR signals for differentiation through a process termed agonist selection. The signaling relationships that underlie these three fates are unknown. RasGRP1 is a Ras activator required to transmit weak TCR signals leading to positive selection. Here, we report that, despite being dispensable for thymocyte clonal deletion, RasGRP1 is critical for agonist selection of TCRαβ+CD8αα intraepithelial lymphocyte (IEL) progenitors (IELps), even though both outcomes require strong TCR signaling. Bim deficiency rescued IELp development in RasGRP1−/− mice, suggesting that RasGRP1 functions to promote survival during IELp generation. Additionally, expression of CD122 and the adhesion molecules α4β7 and CD103 define distinct IELp subsets with differing abilities to generate TCRαβ+CD8αα IEL in vivo. These findings demonstrate that RasGRP1-dependent signaling underpins thymic selection processes induced by both weak and strong TCR signals and is differentially required for fate decisions derived from a strong TCR stimulus.
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Scooped by
Gilbert C FAURE
July 3, 2017 6:49 AM
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In humans, a complex interaction between the host immune system and commensal microbiota is required to maintain gut homeostasis. In this symbiotic relationship, the microbiota provides carbohydrat
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Scooped by
Gilbert C FAURE
July 3, 2017 4:12 AM
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Elsevier's Scopus, the largest abstract and citation database of peer-reviewed literature. Search and access research from the science, technology, medicine, social sciences and arts and humanities fields.
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Scooped by
Gilbert C FAURE
July 2, 2017 6:41 AM
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The microbiota plays a central role in human health and disease by shaping immune development, immune responses and metabolism, and by protecting from invading pathogens. Technical advances tha
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Scooped by
Gilbert C FAURE
July 1, 2017 5:03 AM
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SMI's official journal, Mucosal Immunology, now boasts an impact factor of 7.48! The journal is now ranked 19th of 150 immunology titles.
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Scooped by
Gilbert C FAURE
July 1, 2017 4:59 AM
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Researchers at the Universities of Liverpool and Sheffield have uncovered an unappreciated role for the mucosal host defence protein, BPIFA1/SPLUNC1, in defence against early infection with influenza A.
Influenza A can cause an acute infection of the lungs that can spread easily from person t
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Suggested by
LIGHTING
June 30, 2017 1:47 PM
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Gut homeostasis is a tightly regulated process requiring finely tuned complex interactions between different cell types, growth factors, or cytokines and their receptors. Previous work has implicated a role for IL-6 and mucosal immune cells in intestinal regeneration following injury and in promoting inflammation and cancer. We hypothesized that IL-6 signaling could also modulate crypt homeostasis. Using mouse in vitro crypt organoid and in vivo models, this study first demonstrated that exogenous IL-6 promoted crypt organoid proliferation and increased stem cell numbers through pSTAT3 activation in Paneth cells. Immunolabeling studies showed that the IL-6 receptor was restricted to the basal membrane of Paneth cells both in vitro and in vivo and that the crypt epithelium also expressed IL-6. Either a blocking Ab to the IL-6 receptor or a neutralizing Ab to IL-6 significantly reduced in vitro basal crypt organoid proliferation and budding, and in vivo significantly reduced the number of nuclei and the number of Lgr5EGFP-positive stem cells per crypt compared with IgG-treated mice, with the number of Paneth cells per crypt also significantly reduced. Functional studies demonstrated that IL-6–induced in vitro crypt organoid proliferation and crypt budding was abrogated by the Wnt inhibitor IWP2. This work demonstrates that autocrine IL-6 signaling in the gut epithelium regulates crypt homeostasis through the Paneth cells and the Wnt signaling pathway.
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