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https://www.readbyqxmd.com/read/28428786/challenge-of-humans-with-wild-type-salmonella-enterica-serovar-typhi-elicits-changes-in-the-activation-and-homing-characteristics-of-mucosal-associated-invariant-t-cells
#1
Rosângela Salerno-Goncalves, David Luo, Stephanie Fresnay, Laurence Magder, Thomas C Darton, Claire Jones, Claire S Waddington, Christoph J Blohmke, Brian Angus, Myron M Levine, Andrew J Pollard, Marcelo B Sztein
Gastrointestinal infections by Salmonella enterica serovar Typhi (S. Typhi) are rare in industrialized countries. However, they remain a major public health problem in the developing world with an estimated 26.9 million new cases annually and significant mortality when untreated. Recently, we provided the first direct evidence that CD8(+) MAIT cells are activated and have the potential to kill cells exposed to S. Typhi, and that these responses are dependent on bacterial load. However, MAIT cell kinetics and function during bacterial infections in humans remain largely unknown...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28421059/phages-in-the-human-body
#2
REVIEW
Ferran Navarro, Maite Muniesa
Bacteriophages, viruses that infect bacteria, have re-emerged as powerful regulators of bacterial populations in natural ecosystems. Phages invade the human body, just as they do other natural environments, to such an extent that they are the most numerous group in the human virome. This was only revealed in recent metagenomic studies, despite the fact that the presence of phages in the human body was reported decades ago. The influence of the presence of phages in humans has yet to be evaluated; but as in marine environments, a clear role in the regulation of bacterial populations could be envisaged, that might have an impact on human health...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28419492/expression-and-trafficking-of-mhc-related-protein-1-mr1
#3
REVIEW
R Lamichhane, J E Ussher
MHC related protein 1 (MR1) is a non-polymorphic MHC class IB antigen presenting molecule that is the restricting molecule for mucosal associated invariant T (MAIT) cells, a prominent population of innate-like antibacterial T cells. The MAIT cell-MR1 axis represents a new paradigm in antigen presentation, with the MR1 ligand derived from vitamin B compounds or their metabolic precursors. Many bacteria and some fungi produce the activating ligand for MR1. In evolution, MR1 is highly conserved in most, but not all, mammals...
April 17, 2017: Immunology
https://www.readbyqxmd.com/read/28387217/defective-gpsm2-g%C3%AE-i3-signalling-disrupts-stereocilia-development-and-growth-cone-actin-dynamics-in-chudley-mccullough-syndrome
#4
Stephanie A Mauriac, Yeri E Hien, Jonathan E Bird, Steve Dos-Santos Carvalho, Ronan Peyroutou, Sze Chim Lee, Maite M Moreau, Jean-Michel Blanc, Aysegul Geyser, Chantal Medina, Olivier Thoumine, Sandra Beer-Hammer, Thomas B Friedman, Lukas Rüttiger, Andrew Forge, Bernd Nürnberg, Nathalie Sans, Mireille Montcouquiol
Mutations in GPSM2 cause Chudley-McCullough syndrome (CMCS), an autosomal recessive neurological disorder characterized by early-onset sensorineural deafness and brain anomalies. Here, we show that mutation of the mouse orthologue of GPSM2 affects actin-rich stereocilia elongation in auditory and vestibular hair cells, causing deafness and balance defects. The G-protein subunit Gαi3, a well-documented partner of Gpsm2, participates in the elongation process, and its absence also causes hearing deficits. We show that Gpsm2 defines an ∼200 nm nanodomain at the tips of stereocilia and this localization requires the presence of Gαi3, myosin 15 and whirlin...
April 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28384290/mait-cells-are-reduced-in-frequency-and-functionally-impaired-in-human-t-lymphotropic-virus-type-1-infection-potential-clinical-implications
#5
Dominic Paquin-Proulx, Benjamin C Greenspun, Emanuela A S Costa, Aluisio C Segurado, Esper G Kallas, Douglas F Nixon, Fabio E Leal
HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develop HAM/TSP. The cellular immune response has been implicated in the development of inflammatory alterations in these patients; however the pathogenic mechanisms for disease progression remain unclear. Furthermore, HTLV-1-infected individuals have an increase incidence of Mycobacterium tuberculosis (Mtb) infection, suggesting that immunological defect are associated with HTLV-1 infection...
2017: PloS One
https://www.readbyqxmd.com/read/28378547/deficiencies-of-circulating-mucosal-associated-invariant-t-cells-and-natural-killer-t-cells-in-patients-with-multiple-trauma
#6
Young Goun Jo, Hyun Jung Choi, Jung Chul Kim, Young Nan Cho, Jeong Hwa Kang, Hye Mi Jin, Seung Jung Kee, Yong Wook Park
Mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells are known to play important roles in autoimmunity, infectious diseases and cancers. However, little is known about the roles of these invariant T cells in multiple trauma. The purposes of this study were to examine MAIT and NKT cell levels in patients with multiple trauma and to investigate potential relationships between these cell levels and clinical parameters. The study cohort was composed of 14 patients with multiple trauma and 22 non-injured healthy controls (HCs)...
May 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28370104/recent-advances-in-gut-immunology
#7
Nick Powell, Thomas T MacDonald
In recent years there have been significant advances in our understanding of the mucosal immune system. In addition to unravelling some of the complexities of this system, including the discovery of completely new cells types, further insights into the three way interactions between mucosal immune cells, the intestinal epithelium and the microbial communities colonizing the GI tract, promises to redefine our understanding of how intestinal homeostasis is maintained, but also how dysregulation of these highly integrated interactions conspires to cause disease...
March 31, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28355272/vitamin-d-receptor-gene-is-epigenetically-altered-and-transcriptionally-up-regulated-in-multiple-sclerosis
#8
Teresa Ayuso, Patricia Aznar, Luis Soriano, Ander Olaskoaga, Miren Roldán, María Otano, Iratxe Ajuria, Gerardo Soriano, Francisco Lacruz, Maite Mendioroz
OBJECTIVE: Vitamin D deficiency has been linked to increased risk of multiple sclerosis (MS) and poor outcome. However, the specific role that vitamin D plays in MS still remains unknown. In order to identify potential mechanisms underlying vitamin D effects in MS, we profiled epigenetic changes in vitamin D receptor (VDR) gene to identify genomic regulatory elements relevant to MS pathogenesis. METHODS: Human T cells derived from whole blood by negative selection were isolated in a set of 23 relapsing-remitting MS (RRMS) patients and 12 controls matched by age and gender...
2017: PloS One
https://www.readbyqxmd.com/read/28346544/epigenetic-silencing-of-v-d-j-recombination-is-a-major-determinant-for-selective-differentiation-of-mucosal-associated-invariant-t-cells-from-induced-pluripotent-stem-cells
#9
Yutaka Saito, Chie Sugimoto, Toutai Mituyama, Hiroshi Wakao
Mucosal-associated invariant T cells (MAITs) are innate-like T cells that play a pivotal role in the host defense against infectious diseases, and are also implicated in autoimmune diseases, metabolic diseases, and cancer. Recent studies have shown that induced pluripotent stem cells (iPSCs) derived from MAITs selectively redifferentiate into MAITs without altering their antigen specificity. Such a selective differentiation is a prerequisite for the use of MAITs in cell therapy and/or regenerative medicine...
2017: PloS One
https://www.readbyqxmd.com/read/28328117/noonan-syndrome-ptpn11-mutations-and-brain-tumors-a-clinical-report-and-review-of-the-literature
#10
Aurore Siegfried, Claude Cances, Marie Denuelle, Najat Loukh, Maïté Tauber, Hélène Cavé, Marie-Bernadette Delisle
Noonan syndrome (NS), an autosomal dominant disorder, is characterized by short stature, congenital heart defects, developmental delay, and facial dysmorphism. PTPN11 mutations are the most common cause of NS. PTPN11 encodes a non-receptor protein tyrosine phosphatase, SHP2. Hematopoietic malignancies and solid tumors are associated with NS. Among solid tumors, brain tumors have been described in children and young adults but remain rather rare. We report a 16-year-old boy with PTPN11-related NS who, at the age of 12, was incidentally found to have a left temporal lobe brain tumor and a cystic lesion in the right thalamus...
April 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28303547/persistent-lymphopenia-is-a-risk-factor-for-icu-acquired-infections-and-for-death-in-icu-patients-with-sustained-hypotension-at-admission
#11
Christophe Adrie, Maxime Lugosi, Romain Sonneville, Bertrand Souweine, Stéphane Ruckly, Jean-Charles Cartier, Maité Garrouste-Orgeas, Carole Schwebel, Jean-François Timsit
BACKGROUND: Severely ill patients might develop an alteration of their immune system called post-aggressive immunosuppression. We sought to assess the risk of ICU-acquired infection and of mortality according to the absolute lymphocyte count at ICU admission and its changes over 3 days. METHODS: Adults in ICU for at least 3 days with a shock or persistent low blood pressure were extracted from a French ICU database and included. We evaluated the impact of the absolute lymphocyte count at baseline and its change at day 3 on the incidence of ICU-acquired infection and on the 28-day mortality rate...
December 2017: Annals of Intensive Care
https://www.readbyqxmd.com/read/28288675/activation-status-of-mucosal-associated-invariant-t-cells-reflects-disease-activity-and-pathology-of-systemic-lupus-erythematosus
#12
Asako Chiba, Naoto Tamura, Kazunori Yoshikiyo, Goh Murayama, Mie Kitagaichi, Ken Yamaji, Yoshinari Takasaki, Sachiko Miyake
BACKGROUND: Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes constituting a large proportion of peripheral blood T cells expressing αβ T-cell receptor in humans. In this study, we aimed to investigate their involvement in systemic lupus erythematosus (SLE). METHODS: Peripheral blood MAIT cells from patients with SLE were assessed for their frequency, activation markers, and cell death by flow cytometry. The correlation between plasma cytokine levels and CD69 expression on MAIT cells was analyzed...
March 14, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28272391/stabilizing-short-lived-schiff-base-derivatives-of-5-aminouracils-that-activate-mucosal-associated-invariant-t-cells
#13
Jeffrey Y W Mak, Weijun Xu, Robert C Reid, Alexandra J Corbett, Bronwyn S Meehan, Huimeng Wang, Zhenjun Chen, Jamie Rossjohn, James McCluskey, Ligong Liu, David P Fairlie
Mucosal-associated invariant T (MAIT) cells are activated by unstable antigens formed by reactions of 5-amino-6-D-ribitylaminouracil (a vitamin B2 biosynthetic intermediate) with glycolysis metabolites such as methylglyoxal. Here we show superior preparations of antigens in dimethylsulfoxide, avoiding their rapid decomposition in water (t1/2 1.5 h, 37 °C). Antigen solution structures, MAIT cell activation potencies (EC50 3-500 pM), and chemical stabilities are described. Computer analyses of antigen structures reveal stereochemical and energetic influences on MAIT cell activation, enabling design of a water stable synthetic antigen (EC50 2 nM)...
March 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28265374/erratum-mait-cells-new-guardians-of-the-liver
#14
Ayako Kurioka, Lucy J Walker, Paul Klenerman, Christian B Willberg
[This corrects the article DOI: 10.1038/cti.2016.51.].
February 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28249259/fibroblast-growth-factor-15-19-in-hepatocarcinogenesis
#15
Gloria Alvarez-Sola, Iker Uriarte, M Ujue Latasa, Raquel Urtasun, Marina Bárcena-Varela, Maria Elizalde, Maddalen Jiménez, Carlos M Rodriguez-Ortigosa, Fernando J Corrales, Maite G Fernández-Barrena, Carmen Berasain, Matías A Avila
BACKGROUND: Advanced hepatocellular carcinoma (HCC) is a neoplastic disease with a very bad prognosis and increasing worldwide incidence. HCCs are resistant to conventional chemotherapy and the multikinase inhibitor sorafenib is the only agent that has shown some clinical efficacy. It is therefore important to identify key molecular mechanisms driving hepatocarcinogenesis for the development of more efficacious therapies. However, HCCs are heterogeneous tumors and different molecular subclasses have been characterized...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28223441/rima-dependent-nuclear-accumulation-of-iyo-triggers-auxin-irreversible-cell-differentiation-in-arabidopsis
#16
Alfonso Muñoz, Silvina Mangano, Mary Paz González-García, Ramón Contreras, Michael Sauer, Bert De Rybel, Dolf Weijers, José Juan Sánchez-Serrano, Maite Sanmartín, Enrique Rojo
The transcriptional regulator MINIYO (IYO) is essential and rate-limiting for initiating cell differentiation in Arabidopsis thaliana Moreover, IYO moves from the cytosol into the nucleus in cells at the meristem periphery, possibly triggering their differentiation. However, the genetic mechanisms controlling IYO nuclear accumulation were unknown, and the evidence that increased nuclear IYO levels trigger differentiation remained correlative. Searching for IYO interactors, we identified RPAP2 IYO Mate (RIMA), a homolog of yeast and human proteins linked to nuclear import of selective cargo...
March 2017: Plant Cell
https://www.readbyqxmd.com/read/28179539/smoking-reduces-circulating-cd26-hi-cd161-hi-mait-cells-in-healthy-individuals-and-patients-with-multiple-sclerosis
#17
Cecilie Ammitzbøll, Lars Börnsen, Jeppe Romme Christensen, Rikke Ratzer, Birgitte Romme Nielsen, Helle B Søndergaard, Marina R von Essen, Finn Sellebjerg
Upon chronic cigarette smoke exposure, inhaled antigens and irritants cause altered lung immune homeostasis. Circulating immune cells are affected, and smoking is associated with an increased risk of developing various disorders, including multiple sclerosis (MS). This study was conducted to determine the impact of smoking on circulating immune cell subsets. Furthermore, we determined whether any smoking-associated changes were related to MS. With the use of flow cytometry, CFSE assays, and ELISpot assays, we analyzed circulating immune cell phenotypes and quantified antigen-induced proliferation and cytokine secretion in smokers and nonsmokers in a cohort of 100 healthy individuals (HI)...
February 8, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28166248/characterization-of-three-dimensional-cancer-cell-migration-in-mixed-collagen-matrigel-scaffolds-using-microfluidics-and-image-analysis
#18
María Anguiano, Carlos Castilla, Martin Maška, Cristina Ederra, Rafael Peláez, Xabier Morales, Gorka Muñoz-Arrieta, Maite Mujika, Michal Kozubek, Arrate Muñoz-Barrutia, Ana Rouzaut, Sergio Arana, José Manuel Garcia-Aznar, Carlos Ortiz-de-Solorzano
Microfluidic devices are becoming mainstream tools to recapitulate in vitro the behavior of cells and tissues. In this study, we use microfluidic devices filled with hydrogels of mixed collagen-Matrigel composition to study the migration of lung cancer cells under different cancer invasion microenvironments. We present the design of the microfluidic device, characterize the hydrogels morphologically and mechanically and use quantitative image analysis to measure the migration of H1299 lung adenocarcinoma cancer cells in different experimental conditions...
2017: PloS One
https://www.readbyqxmd.com/read/28166217/drugs-and-drug-like-molecules-can-modulate-the-function-of-mucosal-associated-invariant-t-cells
#19
Andrew N Keller, Sidonia B G Eckle, Weijun Xu, Ligong Liu, Victoria A Hughes, Jeffrey Y W Mak, Bronwyn S Meehan, Troi Pediongco, Richard W Birkinshaw, Zhenjun Chen, Huimeng Wang, Criselle D'Souza, Lars Kjer-Nielsen, Nicholas A Gherardin, Dale I Godfrey, Lyudmila Kostenko, Alexandra J Corbett, Anthony W Purcell, David P Fairlie, James McCluskey, Jamie Rossjohn
The major-histocompatibility-complex-(MHC)-class-I-related molecule MR1 can present activating and non-activating vitamin-B-based ligands to mucosal-associated invariant T cells (MAIT cells). Whether MR1 binds other ligands is unknown. Here we identified a range of small organic molecules, drugs, drug metabolites and drug-like molecules, including salicylates and diclofenac, as MR1-binding ligands. Some of these ligands inhibited MAIT cells ex vivo and in vivo, while others, including diclofenac metabolites, were agonists...
April 2017: Nature Immunology
https://www.readbyqxmd.com/read/28164306/amustaline-s-303-treatment-inactivates-high-levels-of-zika-virus-in-red-blood-cell-components
#20
Andrew Laughhunn, Felicia Santa Maria, Julien Broult, Marion C Lanteri, Adonis Stassinopoulos, Didier Musso, Maite Aubry
BACKGROUND: The potential for Zika virus (ZIKV) transfusion-transmission (TT) has been demonstrated in French Polynesia and Brazil. Pathogen inactivation (PI) of blood products is a proactive strategy to inactivate TT pathogens including arboviruses. Inactivation of West Nile, dengue, Zika, and chikungunya viruses was previously demonstrated by photochemical treatment with amotosalen and ultraviolet A (UVA) illumination. In this study, we evaluated ZIKV inactivation in red blood cell (RBC) components by a chemical approach that uses amustaline (S-303) and glutathione (GSH)...
February 5, 2017: Transfusion
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