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https://www.readbyqxmd.com/read/28632753/mait-cells-launch-a-rapid-robust-and-distinct-hyperinflammatory-response-to-bacterial-superantigens-and-quickly-acquire-an-anergic-phenotype-that-impedes-their-cognate-antimicrobial-function-defining-a-novel-mechanism-of-superantigen-induced-immunopathology
#1
Christopher R Shaler, Joshua Choi, Patrick T Rudak, Arash Memarnejadian, Peter A Szabo, Mauro E Tun-Abraham, Jamie Rossjohn, Alexandra J Corbett, James McCluskey, John K McCormick, Olivier Lantz, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28632133/correction-functionally-diverse-human-t-cells-recognize-non-microbial-antigens-presented-by-mr1
#2
Marco Lepore, Artem Kalinichenko, Salvatore Calogero, Pavanish Kumar, Bhairav Paleja, Mathias Schmaler, Vipin Narang, Francesca Zolezzi, Michael Poidinger, Lucia Mori, Gennaro De Libero
No abstract text is available yet for this article.
June 20, 2017: ELife
https://www.readbyqxmd.com/read/28630305/multiple-layers-of-heterogeneity-and-subset-diversity-in-human-mait-cell-responses-to-distinct-microorganisms-and-to-innate-cytokines
#3
Joana Dias, Edwin Leeansyah, Johan K Sandberg
Mucosa-associated invariant T (MAIT) cells are a large innate-like T-cell subset in humans defined by invariant TCR Vα7.2 use and expression of CD161. MAIT cells recognize microbial riboflavin metabolites of bacterial or fungal origin presented by the monomorphic MR1 molecule. The extraordinary level of evolutionary conservation of MR1 and the limited known diversity of riboflavin metabolite antigens have suggested that MAIT cells are relatively homogeneous and uniform in responses against diverse microbes carrying the riboflavin biosynthesis pathway...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28526582/mait-cells-a-tailor-made-mate-in-the-ancient-battle-against-infectious-diseases
#4
REVIEW
Marcela de Lima Moreira, Moriya Tsuji, Alexandra Jane Corbett, Márcio Sobreira Silva Araújo, Andréa Teixeira-Carvalho, Olindo Assis Martins-Filho, Vanessa Peruhype-Magalhães, Jordana Grazziela Coelho-Dos-Reis
It has been almost two decades since the discovery of mucosal-associated invariant T (MAIT)-cells. Several advances in the field have been made such as the discovery of the antimicrobial activity of MAIT-cells, the abundance of these cells in human mucosa and in liver and the discovery of ligands able to bind MR1 and activate MAIT-cells. MAIT-cells are a unique subset of innate-like T-cells that express a canonical T-cell receptor with the alpha chain containing hAV7S2 and AJ33 in humans (TCRVα7.2Jα33) and respond to bacterial/fungus vitamin B2 metabolites by an MR1-dependent pathway...
May 16, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28518215/the-tlr9-signaling-pathway-regulates-mr1-mediated-bacterial-antigen-presentation-in-b-cells
#5
Jianyun Liu, Randy R Brutkiewicz
Mucosal-associated invariant T (MAIT) cells are conserved T cells that express a semi-invariant TCR (Vα7.2 in humans and Vα19 in mice). The development of MAIT cells requires the antigen (Ag) presenting MHC-related protein 1 (MR1), as well as commensal bacteria. The mechanisms that regulate the functional expression of MR1 molecules and their loading with bacterial Ag in APCs are largely unknown. We have found that treating B cells with the TLR9 agonist CpG increases MR1 surface expression. Interestingly, activation of TLR9 by CpG-A (but not CpG-B) enhances MR1 surface expression...
May 18, 2017: Immunology
https://www.readbyqxmd.com/read/28518056/functionally-diverse-human-t-cells-recognize-non-microbial-antigens-presented-by-mr1
#6
Marco Lepore, Artem Kalinichenko, Salvatore Calogero, Pavanish Kumar, Bhairav Paleja, Mathias Schmaler, Vipin Narang, Francesca Zolezzi, Michael Poidinger, Lucia Mori, Gennaro De Libero
MHC class I-related molecule MR1 presents riboflavin- and folate-related metabolites to mucosal-associated invariant T cells, but it is unknown whether MR1 can present alternative antigens to other T cell lineages. In healthy individuals we identified MR1-restricted T cells (named MR1T cells) displaying diverse TCRs and reacting to MR1-expressing cells in the absence of microbial ligands. Analysis of MR1T cell clones revealed specificity for distinct cell-derived antigens and alternative transcriptional strategies for metabolic programming, cell cycle control and functional polarization following antigen stimulation...
May 18, 2017: ELife
https://www.readbyqxmd.com/read/28494326/mait-cells-and-mr1-antigen-recognition
#7
REVIEW
Andrew N Keller, Alexandra J Corbett, Jacinta M Wubben, James McCluskey, Jamie Rossjohn
Mucosal-associated invariant T cells (MAIT cells) are innate-like T cells that recognise antigens presented by the monomorphic MHC-I related molecule, MR1. Distinct from the conventional MHC-restricted T cell system, MR1 presents small-molecule precursors, derived from microbial biosynthesis of riboflavin, to activate the innate MAIT cell effector potential. Recent data demonstrates how: vitamin B precursors modulate intracellular trafficking of MR1 and impact on MAIT cell development; variation in the MAIT cell antigen receptor sequence impacts MR1-antigen recognition; and most notably, how MR1 can capture chemical identities distinct from riboflavin precursors, including drugs and drug-like molecules...
May 8, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28419492/expression-and-trafficking-of-mr1
#8
REVIEW
Rajesh Lamichhane, James E Ussher
MHC class I-related gene protein (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...
July 2017: Immunology
https://www.readbyqxmd.com/read/28304232/a-systematic-evaluation-of-intraoperative-white-matter-tract-shift-in-pediatric-epilepsy-surgery-using-high-field-mri-and-probabilistic-high-angular-resolution-diffusion-imaging-tractography
#9
Joseph Yuan-Mou Yang, Richard Beare, Marc L Seal, A Simon Harvey, Vicki A Anderson, Wirginia J Maixner
OBJECTIVE Characterization of intraoperative white matter tract (WMT) shift has the potential to compensate for neuronavigation inaccuracies using preoperative brain imaging. This study aimed to quantify and characterize intraoperative WMT shift from the global hemispheric to the regional tract-based scale and to investigate the impact of intraoperative factors (IOFs). METHODS High angular resolution diffusion imaging (HARDI) diffusion-weighted data were acquired over 5 consecutive perioperative time points (MR1 to MR5) in 16 epilepsy patients (8 male; mean age 9...
May 2017: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/28288675/activation-status-of-mucosal-associated-invariant-t-cells-reflects-disease-activity-and-pathology-of-systemic-lupus-erythematosus
#10
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
#11
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/28229332/the-role-of-riboflavin-in-decolourisation-of-congo-red-and-bioelectricity-production-using-shewanella-oneidensis-mr1-under-mfc-and-non-mfc-conditions
#12
Ola M Gomaa, Segun Fapetu, Godfrey Kyazze, Tajalli Keshavarz
Dissimilatory metal reducing bacteria can exchange electrons extracellularly and hold great promise for their use in simultaneous wastewater treatment and electricity production. This study investigated the role of riboflavin, an electron carrier, in the decolourisation of Congo red in microbial fuel cells (MFCs) using Shewanella oneidensis MR-1 as a model organism. The contribution of the membrane-bound protein MtrC to the decolourisation process was also investigated. Within the range of riboflavin concentrations tested, 20 µM was found to be the best with >95% of the dye (initial concentration 200 mg/L) decolourised in MFCs within 50 h compared to 90% in the case where no riboflavin was added...
March 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28177645/conventional-radiographs-and-magnetic-resonance-imaging-for-the-analysis-of-trochlear-dysplasia-the-influence-of-selected-levels-on-magnetic-resonance-imaging
#13
Philippe Matthias Tscholl, Florian Wanivenhaus, Sandro F Fucentese
BACKGROUND: Trochlear dysplasia is one of the most important risk factors for recurrent patellar instability. It is defined on true lateral conventional radiographs (CR) and axial magnetic resonance imaging (MRI). The type of trochlear dysplasia is decisive for surgical treatment; however, low agreement between CR and MRI has been reported. PURPOSE: To compare the Dejour classification of trochlear dysplasia on CR and axial MRI using differing levels defined in the literature...
April 2017: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/28166217/drugs-and-drug-like-molecules-can-modulate-the-function-of-mucosal-associated-invariant-t-cells
#14
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/28090319/the-role-of-liver-sinusoidal-cells-in-local-hepatic-immune-surveillance
#15
REVIEW
Dirk Wohlleber, Percy A Knolle
Although the liver's function as unique immune organ regulating immunity has received a lot of attention over the last years, the mechanisms determining hepatic immune surveillance against infected hepatocytes remain less well defined. Liver sinusoidal cells, in particular, liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs), serve as physical platform for recruitment and anchoring of blood-borne immune cells in the liver. Liver sinusoidal cells also function as portal of entry for infectious microorganisms targeting the liver such as hepatotropic viruses, bacteria or parasites...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27881839/a-polymorphism-in-human-mr1-is-associated-with-mrna-expression-and-susceptibility-to-tuberculosis
#16
C Seshadri, N T T Thuong, N T H Mai, N D Bang, T T H Chau, D M Lewinsohn, G E Thwaites, S J Dunstan, T R Hawn
The MR1 antigen-presenting system is conserved among mammals and enables T cells to recognize small molecules produced by bacterial pathogens, including Mycobacterium tuberculosis (M.tb). However, it is not known whether MR1-mediated antigen presentation is important for protective immunity against mycobacterial disease. We hypothesized that genetic control of MR1 expression correlates with clinical outcomes of tuberculosis infection. We performed an MR1 candidate gene association study and identified an intronic single-nucleotide polymorphism (rs1052632) that was significantly associated with susceptibility to tuberculosis in a discovery and validation cohort of Vietnamese adults with tuberculosis...
January 2017: Genes and Immunity
https://www.readbyqxmd.com/read/27799620/mait-cells-promote-inflammatory-monocyte-differentiation-into-dendritic-cells-during-pulmonary-intracellular-infection
#17
Anda I Meierovics, Siobhán C Cowley
Mucosa-associated invariant T (MAIT) cells are a unique innate T cell subset that is necessary for rapid recruitment of activated CD4(+) T cells to the lungs after pulmonary F. tularensis LVS infection. Here, we investigated the mechanisms behind this effect. We provide evidence to show that MAIT cells promote early differentiation of CCR2-dependent monocytes into monocyte-derived DCs (Mo-DCs) in the lungs after F. tularensis LVS pulmonary infection. Adoptive transfer of Mo-DCs to MAIT cell-deficient mice (MR1(-/-) mice) rescued their defect in the recruitment of activated CD4(+) T cells to the lungs...
November 14, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27759023/mr1-restricted-mucosal-associated-invariant-t-mait-cells-respond-to-mycobacterial-vaccination-and-infection-in-nonhuman-primates
#18
J M Greene, P Dash, S Roy, C McMurtrey, W Awad, J S Reed, K B Hammond, S Abdulhaqq, H L Wu, B J Burwitz, B F Roth, D W Morrow, J C Ford, G Xu, J Y Bae, H Crank, A W Legasse, T H Dang, H Y Greenaway, M Kurniawan, M C Gold, M J Harriff, D A Lewinsohn, B S Park, M K Axthelm, J J Stanton, S G Hansen, L J Picker, V Venturi, W Hildebrand, P G Thomas, D M Lewinsohn, E J Adams, J B Sacha
Studies on mucosal-associated invariant T cells (MAITs) in nonhuman primates (NHP), a physiologically relevant model of human immunity, are handicapped due to a lack of macaque MAIT-specific reagents. Here we show that while MR1 ligand-contact residues are conserved between human and multiple NHP species, three T-cell receptor contact-residue mutations in NHP MR1 diminish binding of human MR1 tetramers to macaque MAITs. Construction of naturally loaded macaque MR1 tetramers facilitated identification and characterization of macaque MR1-binding ligands and MAITs, both of which mirrored their human counterparts...
May 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/27704611/variation-in-taper-surface-roughness-for-a-single-design-effects-the-wear-rate-in-total-hip-arthroplasty
#19
Robert K Whittaker, Harry S Hothi, Antti Eskelinen, Gordon W Blunn, John A Skinner, Alister J Hart
Material loss from the head-stem taper junction of total hip arthroplasty (THA) is implicated in adverse reactions to metal debris (ARMD); the mechanisms for this are multi-factorial. We investigated the relationship between the roughness of the "as manufactured" taper surface and the wear rate from this junction. Fifty retrieved Pinnacle metal-on-metal (MOM) bearings paired with a Corail stem were included in the study. Multivariable statistical analysis was performed to determine the influence of taper roughness on material loss rate after controlling for other confounding surgical, implant, and patient factors...
October 5, 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/27694276/dynamic-contrast-enhanced-mri-measurement-of-renal-function-in-healthy-participants
#20
Eli Eikefjord, Erling Andersen, Erlend Hodneland, Erik A Hanson, Steven Sourbron, Einar Svarstad, Arvid Lundervold, Jarle T Rørvik
Background High repeatability, accuracy, and precision for renal function measurements need to be achieved to establish renal dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as a clinically useful diagnostic tool. Purpose To investigate the repeatability, accuracy, and precision of DCE-MRI measured renal perfusion and glomerular filtration rate (GFR) using iohexol-GFR as the reference method. Material and Methods Twenty healthy non-smoking volunteers underwent repeated DCE-MRI and an iohexol-GFR within a period of 10 days...
June 2017: Acta Radiologica
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