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https://www.readbyqxmd.com/read/28087239/on-going-mechanical-damage-from-mastication-drives-homeostatic-th17-cell-responses-at-the-oral-barrier
#1
Nicolas Dutzan, Loreto Abusleme, Hayley Bridgeman, Teresa Greenwell-Wild, Tamsin Zangerle-Murray, Mark E Fife, Nicolas Bouladoux, Holly Linley, Laurie Brenchley, Kelly Wemyss, Gloria Calderon, Bo-Young Hong, Timothy J Break, Dawn M E Bowdish, Michail S Lionakis, Simon A Jones, Giorgio Trinchieri, Patricia I Diaz, Yasmine Belkaid, Joanne E Konkel, Niki M Moutsopoulos
Immuno-surveillance networks operating at barrier sites are tuned by local tissue cues to ensure effective immunity. Site-specific commensal bacteria provide key signals ensuring host defense in the skin and gut. However, how the oral microbiome and tissue-specific signals balance immunity and regulation at the gingiva, a key oral barrier, remains minimally explored. In contrast to the skin and gut, we demonstrate that gingiva-resident T helper 17 (Th17) cells developed via a commensal colonization-independent mechanism...
January 6, 2017: Immunity
https://www.readbyqxmd.com/read/28080210/pathogen-control-at-the-intestinal-mucosa-h2o2-to-the-rescue
#2
Ulla G Knaus, Rosanne Hertzberger, Gratiela G Pircalabioru, S Parsa M Yousefi, Filipe Branco Dos Santos
Intestinal infections are a global challenge, connected to malnutrition and inadequate hygiene in developing countries, and to expanding antibiotic resistance in developed countries. In general, a healthy host is capable of fighting off gut pathogens or at least to recover from infections quickly. The underlying protective mechanism, termed colonization resistance, is provided by indigenous commensal communities (microbiota) that are shaped and aided by the host's epithelial and innate immune system. (1) Commensal-pathogen interactions are governed by competition for a suitable niche for replication and stable colonization, nutrient availability, species-specific alterations of the metabolic environment, changes in oxygen tension and release of chemicals and proteinaceous toxins (bacteriocins)...
January 12, 2017: Gut Microbes
https://www.readbyqxmd.com/read/28074024/whole-genome-sequencing-of-invasion-resistant-cells-identifies-laminin-%C3%AE-2-as-a-host-factor-for-bacterial-invasion
#3
Xander M van Wijk, Simon Döhrmann, Björn M Hallström, Shangzhong Li, Bjørn G Voldborg, Brandon X Meng, Karen K McKee, Toin H van Kuppevelt, Peter D Yurchenco, Bernhard O Palsson, Nathan E Lewis, Victor Nizet, Jeffrey D Esko
: To understand the role of glycosaminoglycans in bacterial cellular invasion, xylosyltransferase-deficient mutants of Chinese hamster ovary (CHO) cells were created using clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated gene 9 (CRISPR-cas9) gene targeting. When these mutants were compared to the pgsA745 cell line, a CHO xylosyltransferase mutant generated previously using chemical mutagenesis, an unexpected result was obtained. Bacterial invasion of pgsA745 cells by group B Streptococcus (GBS), group A Streptococcus, and Staphylococcus aureus was markedly reduced compared to the invasion of wild-type cells, but newly generated CRISPR-cas9 mutants were only resistant to GBS...
January 10, 2017: MBio
https://www.readbyqxmd.com/read/28069814/muc2-mucin-and-butyrate-contribute-to-the-synthesis-of-the-antimicrobial-peptide-cathelicidin-in-response-to-e-histolytica-and-dss-induced-colitis
#4
Eduardo R Cobo, Vanessa Kissoon-Singh, France Moreau, Ravi Holani, Kris Chadee
Embedded in the colonic mucus are cathelicidins, small cationic peptides secreted by colonic epithelial cells. Humans and mice have one cathelicidin-related antimicrobial peptide (CRAMP), LL-37/hCAP-18 and Cramp respectively, with related structure and functions. Altered production of MUC2 mucin and antimicrobial peptides is characteristic of intestinal amebiasis. The interactions between MUC2 mucin and cathelicidins in conferring innate immunity against Entamoeba histolytica (Eh) are not well characterized...
January 9, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28069747/a-targeted-rnai-screen-identifies-factors-affecting-diverse-stages-of-receptor-mediated-transcytosis
#5
Bradlee Nelms, Natasha Furtado Dalomba, Wayne Lencer
Endosome transport by transcytosis is the primary mechanism by which proteins and other large cargo traverse epithelial barriers in normal tissue. Transcytosis is also essential for establishing and maintaining membrane polarity in epithelia and other polarized cells. To identify novel components of this pathway, we conducted a high-throughput RNA interference screen for factors necessary for the bidirectional transcytosis of IgG by the Fcγ receptor FcRn. This screen identified 23 genes whose suppression resulted in a reproducible decrease in FcRn-mediated transcytosis...
January 9, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28069576/dysbiosis-and-zonulin-upregulation-alter-gut-epithelial-and-vascular-barriers-in-patients-with-ankylosing-spondylitis
#6
Francesco Ciccia, Giuliana Guggino, Aroldo Rizzo, Riccardo Alessandro, Michele Maria Luchetti, Simon Milling, Laura Saieva, Heleen Cypers, Tommaso Stampone, Paola Di Benedetto, Armando Gabrielli, Alessio Fasano, Dirk Elewaut, Giovanni Triolo
BACKGROUND: Dysbiosis has been recently demonstrated in patients with ankylosing spondylitis (AS) but its implications in the modulation of intestinal immune responses have never been studied. The aim of this study was to investigate the role of ileal bacteria in modulating local and systemic immune responses in AS. METHODS: Ileal biopsies were obtained from 50 HLA-B27(+) patients with AS and 20 normal subjects. Silver stain was used to visualise bacteria. Ileal expression of tight and adherens junction proteins was investigated by TaqMan real-time (RT)-PCR and immunohistochemistry...
January 9, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28068384/hypoxia-regulates-mtorc1-mediated-keratinocyte-motility-and-migration-via-the-ampk-pathway
#7
Tiantian Yan, Junhui Zhang, Di Tang, Xingyue Zhang, Xupin Jiang, Liping Zhao, Qiong Zhang, Dongxia Zhang, Yuesheng Huang
Keratinocyte migration, the initial event and rate-limiting step in wound healing, plays a vital role in restoration of the intact skin barrier, also known as re-epithelialization. After acute tissue injury, hypoxic microenvironment gradually develops and acts as an early stimulus to initiate the healing process. Although we have previously found that hypoxia induces keratinocyte migration, the underlying mechanism remains unknown. Here, we first observed that hypoxia increased mTORC1 activity. Recombinant lentivirus vector and Rapamycin were used for silencing mTORC1 in HaCaT cells and primary mouse keratinocytes (MKs)...
2017: PloS One
https://www.readbyqxmd.com/read/28066889/enteric-glial-activity-regulates-secretomotor-function-in-the-mouse-colon-but-does-not-acutely-affect-gut-permeability
#8
Vladimir Grubišić, Brian D Gulbransen
Enteric glial cells are often implicated in the regulation of epithelial barrier and secretomotor functions of the intestines. But whether glial cell activity regulates these functions acutely under physiological conditions is not clear. We addressed this issue by using transgenic animal models to modify the activity of enteric glia, either reducing glial expression of connexin 43 in Sox10::CreER(T2+/-) /Cx43(f/f) mice or activating glial calcium responses in GFAP::hM3Dq mice, and tested the effects on colonic barrier function and electrogenic ion transport in Ussing chambers...
January 8, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28066800/cd36-deficiency-impairs-the-small-intestinal-barrier-and-induces-subclinical-inflammation-in-mice
#9
Vincenza Cifarelli, Stoyan Ivanov, Yan Xie, Ni-Huiping Son, Brian T Saunders, Terri A Pietka, Trevor M Shew, Jun Yoshino, Sinju Sundaresan, Nicholas O Davidson, Ira J Goldberg, Andrew E Gelman, Bernd H Zinselmeyer, Gwendalyn J Randolph, Nada A Abumrad
BACKGROUND & AIMS: CD36 has immuno-metabolic actions and is abundant in the small intestine on epithelial, endothelial and immune cells. We examined the role of CD36 in gut homeostasis using mice null for CD36 (CD36KO) and with CD36 deletion specific to enterocytes (Ent-CD36KO) or endothelial cells (EC-CD36KO). METHODS: Intestinal morphology was evaluated using immunohistochemistry and electron microscopy (EM). Intestinal inflammation was determined from neutrophil infiltration and expression of cytokines, toll-like receptors and COX-2...
January 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28065642/mesenchymal-to-epithelial-transition-mediated-by-cdh1-promotes-spontaneous-reprogramming-of-male-germline-stem-cells-to-pluripotency
#10
Junhui An, Yu Zheng, Christina Tenenhaus Dann
Cultured spermatogonial stem cells (GSCs) can spontaneously form pluripotent cells in certain culture conditions. However, GSC reprogramming is a rare event that is largely unexplained. We show GSCs have high expression of mesenchymal to epithelial transition (MET) suppressors resulting in a developmental barrier inhibiting GSC reprogramming. Either increasing OCT4 or repressing transforming growth factor β (TGF-β) signaling promotes GSC reprogramming by upregulating CDH1 and boosting MET. Reducing ZEB1 also enhances GSC reprogramming through its direct effect on CDH1...
December 24, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/28063049/isolation-and-flow-cytometry-analysis-of-innate-lymphoid-cells-from-the-intestinal-lamina-propria
#11
Konrad Gronke, Michael Kofoed-Nielsen, Andreas Diefenbach
The intestinal mucosa constitutes the biggest surface area of the body. It is constantly challenged by bacteria, commensal and pathogenic, protozoa, and food-derived irritants. In order to maintain homeostasis, a complex network of signaling circuits has evolved that includes contributions of immune cells. In recent years a subset of lymphocytes, which belong to the innate immune system, has caught particular attention. These so-called innate lymphoid cells (ILC) reside within the lamina propria of the small and large intestines and rapidly respond to environmental challenges...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28063035/monitoring-skin-dendritic-cells-in-steady-state-and-inflammation-by-immunofluorescence-microscopy-and-flow-cytometry
#12
Julia L Ober-Blöbaum, Daniela Ortner, Bernhard Haid, Anna Brand, Christoph Tripp, Björn E Clausen, Patrizia Stoitzner
Skin dendritic cells (DC) are strategically positioned at the body's second largest epithelial border to the environment. Hence they are the first antigen presenting cells that encounter invading pathogens and environmental antigens, including contact sensitizers and carcinogens penetrating the skin. Moreover, DC have the unique ability to induce immunity or tolerance and thus take center stage in regulating innate and adaptive immune responses. Skin DC can be divided into several phenotypically and functionally distinct subtypes...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28062847/the-mucosal-barrier-at-a-glance
#13
REVIEW
Marion M France, Jerrold R Turner
Mucosal barriers separate self from non-self and are essential for life. These barriers, which are the first line of defense against external pathogens, are formed by epithelial cells and the substances they secrete. Rather than an absolute barrier, epithelia at mucosal surfaces must allow selective paracellular flux that discriminates between solutes and water while preventing the passage of bacteria and toxins. In vertebrates, tight junctions seal the paracellular space; flux across the tight junction can occur through two distinct routes that differ in selectivity, capacity, molecular composition and regulation...
January 6, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28062701/widespread-virus-replication-in-alveoli-drives-acute-respiratory-distress-syndrome-in-aerosolized-h5n1-influenza-infection-of-macaques
#14
Elizabeth R Wonderlich, Zachary D Swan, Stephanie J Bissel, Amy L Hartman, Jonathan P Carney, Katherine J O'Malley, Adebimpe O Obadan, Jefferson Santos, Reagan Walker, Timothy J Sturgeon, Lonnie J Frye, Pauline Maiello, Charles A Scanga, Jennifer D Bowling, Anthea L Bouwer, Parichat A Duangkhae, Clayton A Wiley, JoAnne L Flynn, Jieru Wang, Kelly S Cole, Daniel R Perez, Douglas S Reed, Simon M Barratt-Boyes
Human infections with highly pathogenic avian influenza A (H5N1) virus are frequently fatal but the mechanisms of disease remain ill-defined. H5N1 infection is associated with intense production of proinflammatory cytokines, but whether this cytokine storm is the main cause of fatality or is a consequence of extensive virus replication that itself drives disease remains controversial. Conventional intratracheal inoculation of a liquid suspension of H5N1 influenza virus in nonhuman primates likely results in efficient clearance of virus within the upper respiratory tract and rarely produces severe disease...
January 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28062699/cathelicidin-wa-improves-intestinal-epithelial-barrier-function-and-enhances-host-defense-against-enterohemorrhagic-escherichia-coli-o157-h7-infection
#15
Hongbo Yi, Wangyang Hu, Shan Chen, Zeqing Lu, Yizhen Wang
Impaired epithelial barrier function disrupts immune homeostasis and increases inflammation in intestines, leading to many intestinal diseases. Cathelicidin peptides suppress intestinal inflammation and improve intestinal epithelial barrier function independently of their antimicrobial activity. In this study, we investigated the effects of Cathelicidin-WA (CWA) on intestinal epithelial barrier function, as well as the underlying mechanism, by using enterohemorrhagic Escherichia coli (EHEC)-infected mice and intestinal epithelial cells...
January 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28062270/the-role-of-gut-microbiota-in-health-and-disease-in%C3%A2-vitro-modeling-of-host-microbe-interactions-at-the-aerobe-anaerobe-interphase-of-the-human-gut
#16
REVIEW
Julius Z H von Martels, Mehdi Sadaghian Sadabad, Arno R Bourgonje, Tjasso Blokzijl, Gerard Dijkstra, Klaas Nico Faber, Hermie J M Harmsen
The microbiota of the gut has many crucial functions in human health. Dysbiosis of the microbiota has been correlated to a large and still increasing number of diseases. Recent studies have mostly focused on analyzing the associations between disease and an aberrant microbiota composition. Functional studies using (in vitro) gut models are required to investigate the precise interactions that occur between specific bacteria (or bacterial mixtures) and gut epithelial cells. As most gut bacteria are obligate or facultative anaerobes, studying their effect on oxygen-requiring human gut epithelial cells is technically challenging...
January 3, 2017: Anaerobe
https://www.readbyqxmd.com/read/28061353/created-of-warm-blood-and-nerves-restoring-an-enteric-nervous-system-in-organoids
#17
Christopher R Schlieve, Tracy C Grikscheit
The enteric nervous system (ENS) regulates numerous gastrointestinal functions, including epithelial barrier permeability and motility. In a recent Nature Medicine study, Workman et al. (2016) propose a method for introducing human pluripotent stem cell-derived enteric neural crest cells into developing human intestinal organoids, thereby restoring ENS cell types and contractile function.
January 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28060943/farnesoid-x-receptor-activation-attenuates-intestinal-ischemia-reperfusion-injury-in-rats
#18
Laurens J Ceulemans, Len Verbeke, Jean-Paul Decuypere, Ricard Farré, Gert De Hertogh, Kaatje Lenaerts, Ina Jochmans, Diethard Monbaliu, Frederik Nevens, Jan Tack, Wim Laleman, Jacques Pirenne
INTRODUCTION: The farnesoid X receptor (FXR) is abundantly expressed in the ileum, where it exerts an enteroprotective role as a key regulator of intestinal innate immunity and homeostasis, as shown in pre-clinical models of inflammatory bowel disease. Since intestinal ischemia reperfusion injury (IRI) is characterized by hyperpermeability, bacterial translocation and inflammation, we aimed to investigate, for the first time, if the FXR-agonist obeticholic acid (OCA) could attenuate intestinal ischemia reperfusion injury...
2017: PloS One
https://www.readbyqxmd.com/read/28060924/the-effector-domain-region-of-the-vibrio-vulnificus-martx-toxin-confers-biphasic-epithelial-barrier-disruption-and-is-essential-for-systemic-spread-from-the-intestine
#19
Hannah E Gavin, Nike T Beubier, Karla J F Satchell
Vibrio vulnificus causes highly lethal bacterial infections in which the Multifunctional Autoprocessing Repeats-in-Toxins (MARTX) toxin product of the rtxA1 gene is a key virulence factor. MARTX toxins are secreted proteins up to 5208 amino acids in size. Conserved MARTX N- and C-terminal repeat regions work in concert to form pores in eukaryotic cell membranes, through which the toxin's central region of modular effector domains is translocated. Upon inositol hexakisphosphate-induced activation of the of the MARTX cysteine protease domain (CPD) in the eukaryotic cytosol, effector domains are released from the holotoxin by autoproteolytic activity...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28057514/systemic-effects-of-subtilase-cytotoxin-produced-by-escherichia-coli-o113-h21
#20
E Abril Seyahian, Gisela Oltra, Federico Ochoa, Santiago Melendi, Ricardo Hermes, James C Paton, Adrienne W Paton, Nestor Lago, Mauricio Castro Parodi, Alicia Damiano, Cristina Ibarra, Elsa Zotta
: Subtilase cytotoxin (SubAB) is a member of the AB5 cytotoxin family and is produced by certain strains of Shiga toxigenic Escherichia coli. The toxin is known to be lethal to mice, but the pathological mechanisms that contribute to Uremic Hemolytic Syndrome (HUS) are poorly understood. In this study we show that intraperitoneal injection of a sublethal dose of SubAB in rats triggers a systemic response, with ascitic fluid accumulation, heart hypertrophy and damage to the liver, colon and kidney...
January 2, 2017: Toxicon: Official Journal of the International Society on Toxinology
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