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https://www.readbyqxmd.com/read/27926862/vav-proteins-are-key-regulators-of-card9-signaling-for-innate-antifungal-immunity
#1
Susanne Roth, Hanna Bergmann, Martin Jaeger, Assa Yeroslaviz, Konstantin Neumann, Paul-Albert Koenig, Clarissa Prazeres da Costa, Lesley Vanes, Vinod Kumar, Melissa Johnson, Mauricio Menacho-Márquez, Bianca Habermann, Victor L Tybulewicz, Mihai Netea, Xosé R Bustelo, Jürgen Ruland
Fungal infections are major causes of morbidity and mortality, especially in immunocompromised individuals. The innate immune system senses fungal pathogens through Syk-coupled C-type lectin receptors (CLRs), which signal through the conserved immune adaptor Card9. Although Card9 is essential for antifungal defense, the mechanisms that couple CLR-proximal events to Card9 control are not well defined. Here, we identify Vav proteins as key activators of the Card9 pathway. Vav1, Vav2, and Vav3 cooperate downstream of Dectin-1, Dectin-2, and Mincle to engage Card9 for NF-κB control and proinflammatory gene transcription...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27923071/c-type-lectin-mincle-recognizes-glucosyl-diacylglycerol-of-streptococcus-pneumoniae-and-plays-a-protective-role-in-pneumococcal-pneumonia
#2
Friederike Behler-Janbeck, Tomotsugu Takano, Regina Maus, Jennifer Stolper, Danny Jonigk, Meritxell Tort Tarrés, Thomas Fuehner, Antje Prasse, Tobias Welte, Mattie S M Timmer, Bridget L Stocker, Yoichi Nakanishi, Tomofumi Miyamoto, Sho Yamasaki, Ulrich A Maus
Among various innate immune receptor families, the role of C-type lectin receptors (CLRs) in lung protective immunity against Streptococcus pneumoniae (S. pneumoniae) is not fully defined. We here show that Mincle gene expression was induced in alveolar macrophages and neutrophils in bronchoalveolar lavage fluids of mice and patients with pneumococcal pneumonia. Moreover, S. pneumoniae directly triggered Mincle reporter cell activation in vitro via its glycolipid glucosyl-diacylglycerol (Glc-DAG), which was identified as the ligand recognized by Mincle...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27855374/inflammatory-properties-and-adjuvant-potential-of-synthetic-glycolipids-homologous-to-mycolate-esters-of-the-cell-wall-of-mycobacterium-tuberculosis
#3
Hermann Giresse Tima, Juma''a Raheem Al Dulayymi, Olivier Denis, Pauline Lehebel, Klarah Sherzad Baols, Mohsin Omar Mohammed, Laurent L'Homme, Mohaned Mohammed Sahb, Georges Potemberg, Sylvie Legrand, Roland Lang, Rudi Beyaert, Jacques Piette, Mark Stephen Baird, Kris Huygen, Marta Romano
The cell wall of mycobacteria is characterised by glycolipids composed of different classes of mycolic acids (MAs; alpha-, keto-, and methoxy-) and sugars (trehalose, glucose, and arabinose). Studies using mutant Mtb strains have shown that the structure of MAs influences the inflammatory potential of these glycolipids. As mutant Mtb strains possess a complex mixture of glycolipids, we analysed the inflammatory potential of single classes of mycolate esters of the Mtb cell wall using 38 different synthetic analogues...
November 18, 2016: Journal of Innate Immunity
https://www.readbyqxmd.com/read/27845194/human-albumin-attenuates-excessive-innate-immunity-via-inhibition-of-microglial-mincle-syk-signaling-in-subarachnoid-hemorrhage
#4
Yi Xie, Hongquan Guo, Liumin Wang, Lili Xu, Xiaohao Zhang, Linjie Yu, Qian Liu, Yunzi Li, Nana Zhao, Nan Zhao, Ruidong Ye, Xinfeng Liu
Subarachnoid hemorrhage (SAH) is a devastating subtype of stroke. Microglial macrophage-inducible C-type lectin (Mincle) receptor launches microglial innate immunity after SAH, and thereby achieves a key step of early cerebral injury in SAH. We previously revealed albumin could improve long-term neurological outcomes after SAH. In this study, we examined the role of microglia-mediated innate immunity in the salutary effects of albumin. SAH was induced by endovascular perforation in rats. We found that albumin can significantly mitigate early neurovascular dysfunction of SAH rats...
November 10, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27790218/stat6-dependent-inhibition-of-mincle-expression-in-mouse-and-human-antigen-presenting-cells-by-the-th2-cytokine-il-4
#5
Thomas Hupfer, Judith Schick, Katrin Jozefowski, David Voehringer, Jenny Ostrop, Roland Lang
The C-type lectin receptors (CLRs) Mincle, Mcl, and Dectin-2 bind mycobacterial and fungal cell wall glycolipids and carbohydrates. Recently, we described that expression of these CLR is downregulated during differentiation of human monocytes to dendritic cells (DC) in the presence of GM-CSF and IL-4. Here, we demonstrate that the Th2 cytokine IL-4 specifically inhibits expression of Mincle, Mcl, and Dectin-2 in human antigen-presenting cells (APC). This inhibitory effect of IL-4 was observed across species, as murine macrophages and DC treated with IL-4 also downregulated these receptors...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27780012/lectin-receptors-expressed-on-myeloid-cells
#6
Gordon D Brown, Paul R Crocker
Lectins recognize a diverse array of carbohydrate structures and perform numerous essential biological functions. Here we focus on only two families of lectins, the Siglecs and C-type lectins. Triggering of intracellular signaling cascades following ligand recognition by these receptors can have profound effects on the induction and modulation of immunity. In this chapter, we provide a brief overview of each family and then focus on selected examples that highlight how these lectins can influence myeloid cell functioning in health and disease...
October 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/27743706/cord-factor-as-an-invisibility-cloak-a-hypothesis-for-asymptomatic-tb-persistence
#7
Robert L Hunter, Shen-An Hwang, Chinnaswamy Jagannath, Jeffrey K Actor
Mycobacterium tuberculosis (MTB) has long been known to persist in grossly normal tissues even in people with active lesions and granulomas in other parts of the body. We recently reported that post-primary TB begins as an asymptomatic infection that slowly progresses, accumulating materials for a massive necrotizing reaction that results in cavitation. This paper explores the possible roles of trehalose 6,6' dimycolate (TDM) or cord factor in the ability of MTB to persist in such lesions without producing inflammation...
September 28, 2016: Tuberculosis
https://www.readbyqxmd.com/read/27742545/leishmania-uses-mincle-to-target-an-inhibitory-itam-signaling-pathway-in-dendritic-cells-that-dampens-adaptive-immunity-to-infection
#8
Salvador Iborra, María Martínez-López, Francisco J Cueto, Ruth Conde-Garrosa, Carlos Del Fresno, Helena M Izquierdo, Clare L Abram, Daiki Mori, Yolanda Campos-Martín, Rosa María Reguera, Benjamin Kemp, Sho Yamasaki, Matthew J Robinson, Manuel Soto, Clifford A Lowell, David Sancho
C-type lectin receptors sense a diversity of endogenous and exogenous ligands that may trigger differential responses. Here, we have found that human and mouse Mincle bind to a ligand released by Leishmania, a eukaryote parasite that evades an effective immune response. Mincle-deficient mice had milder dermal pathology and a tenth of the parasite burden compared to wild-type mice after Leishmania major intradermal ear infection. Mincle deficiency enhanced adaptive immunity against the parasite, correlating with increased activation, migration, and priming by Mincle-deficient dendritic cells (DCs)...
October 18, 2016: Immunity
https://www.readbyqxmd.com/read/27714279/lipid-structure-influences-the-ability-of-glucose-monocorynomycolate-to-signal-through-mincle
#9
Phillip L van der Peet, Masahiro Nagata, Sayali Shah, Jonathan M White, Sho Yamasaki, Spencer J Williams
Mincle (macrophage-inducible C-type lectin) is a C-type lectin receptor that provides the capacity for immune sensing of a range of pathogen- and commensal-derived glycolipids. Mincle can recognize mycolic and/or corynomycolic acid esters of trehalose, glycerol and glucose from mycobacteria and corynebacteria. While simple straight-chain long fatty acids (e.g. behenic acid) can substitute for mycolic acid on trehalose and glycerol and maintain robust signalling through Mincle, glucose monobehenate has been reported to be much less active than glucose monocorynomycolate (GMCM)...
October 4, 2016: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/27628766/irakm-mincle-axis-links-cell-death-to-inflammation-pathophysiological-implications-for-chronic-alcoholic-liver-disease
#10
Hao Zhou, Minjia Yu, Junjie Zhao, Bradley N Martin, Sanjoy Roychowdhury, Megan R McMullen, Emily Wang, Paul L Fox, Sho Yamasaki, Laura E Nagy, Xiaoxia Li
: Lipopolysaccharide (LPS)-mediated activation of Toll-like receptors (TLRs) in hepatic macrophages and injury to hepatocytes are major contributors to the pathogenesis of alcoholic liver disease. However, the mechanisms by which TLR-dependent inflammatory responses and alcohol-induced hepatocellular damage coordinately lead to alcoholic liver disease are not completely understood. In this study, we found that mice deficient in interleukin-1 receptor-associated kinase M (IRAKM), a proximal TLR pathway molecule typically associated with inhibition of TLR signaling, were actually protected from chronic ethanol-induced liver injury...
December 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27559045/mincle-signaling-promotes-con-a-hepatitis
#11
Stephanie H Greco, Alejandro Torres-Hernandez, Aleksandr Kalabin, Clint Whiteman, Rae Rokosh, Sushma Ravirala, Atsuo Ochi, Johana Gutierrez, Muhammad Atif Salyana, Vishnu R Mani, Savitha V Nagaraj, Michael Deutsch, Lena Seifert, Donnele Daley, Rocky Barilla, Mautin Hundeyin, Yuriy Nikifrov, Karla Tejada, Bruce E Gelb, Steven C Katz, George Miller
Con A hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor that is critical in the immune response to mycobacteria and fungi but does not have a well-defined role in preclinical models of non-pathogen-mediated inflammation. Because Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con A hepatitis. Acute liver injury was assessed in the murine Con A hepatitis model using C57BL/6, Mincle(-/-), and Dectin-1(-/-) mice...
October 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27542410/binding-sites-for-acylated-trehalose-analogs-of-glycolipid-ligands-on-an-extended-carbohydrate-recognition-domain-of-the-macrophage-receptor-mincle
#12
Hadar Feinberg, Neela D S Rambaruth, Sabine A F Jégouzo, Kristian M Jacobsen, Rasmus Djurhuus, Thomas B Poulsen, William I Weis, Maureen E Taylor, Kurt Drickamer
The macrophage receptor mincle binds to trehalose dimycolate on the surface of Mycobacterium tuberculosis Signaling initiated by this interaction leads to cytokine production, which underlies the ability of mycobacteria to evade the immune system and also to function as adjuvants. In previous work the mechanism for binding of the sugar headgroup of trehalose dimycolate to mincle has been elucidated, but the basis for enhanced binding to glycolipid ligands, in which hydrophobic substituents are attached to the 6-hydroxyl groups, has been the subject of speculation...
September 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27533919/total-synthesis-of-a-cyclopropane-fatty-acid-%C3%AE-glucosyl-diglyceride-from-lactobacillus-plantarum-and-identification-of-its-ability-to-signal-through-mincle
#13
Sayali Shah, Masahiro Nagata, Sho Yamasaki, Spencer J Williams
We report a concise synthesis of glycolipid GL1 from Lactobacillus plantarum commencing from methyl α-d-glucopyroside. A Jacobsen hydrolytic kinetic resolution is used to generate a diastereomerically-pure glycidyl glucoside that was elaborated to the diglyceride by stepwise brominolysis, acylation with oleoyl chloride, and bromide-substitution by the tetrabutylammonium salt of 9S,10R-dihydrosterculic acid. GL1 and analogues were shown to signal through the glycolipid pattern recognition receptor Mincle.
September 18, 2016: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/27492949/an-atypical-role-for-the-myeloid-receptor-mincle-in-central-nervous-system-injury
#14
Thiruma V Arumugam, Silvia Manzanero, Milena Furtado, Patrick J Biggins, Yu-Hsuan Hsieh, Mathias Gelderblom, Kelli Pa MacDonald, Ekaterina Salimova, Yu-I Li, Othmar Korn, Deborah Dewar, I Mhairi Macrae, Robert B Ashman, Sung-Chun Tang, Nadia A Rosenthal, Marc J Ruitenberg, Tim Magnus, Christine A Wells
The C-type lectin Mincle is implicated in innate immune responses to sterile inflammation, but its contribution to associated pathologies is not well understood. Herein, we show that Mincle exacerbates neuronal loss following ischemic but not traumatic spinal cord injury. Loss of Mincle was beneficial in a model of transient middle cerebral artery occlusion but did not alter outcomes following heart or gut ischemia. High functional scores in Mincle KO animals using the focal cerebral ischemia model were accompanied by reduced lesion size, fewer infiltrating leukocytes and less neutrophil-derived cytokine production than isogenic controls...
August 4, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27363694/polymorphisms-in-the-pattern-recognition-receptor-mincle-gene-clec4e-and-association-with-tuberculosis
#15
Nicholas Bowker, Muneeb Salie, Haiko Schurz, Paul D van Helden, Craig J Kinnear, Eileen G Hoal, Marlo Möller
The mechanisms involved in interactions between Mycobacterium tuberculosis and host innate immune cells determine outcome. Antigen-presenting cells, including macrophages and dendritic cells, express many pattern recognition receptors to identify pathogen-associated molecular patterns, thereby initiating an immune response. A major mycobacterial virulence factor, trehalose-6',6-dimycolate, is recognised by the macrophage-inducible C-type lectin, Mincle, which leads to the activation of the Syk-Card9 signalling pathway in macrophages...
October 2016: Lung
https://www.readbyqxmd.com/read/27252171/trehalose-diester-glycolipids-are-superior-to-the-monoesters-in-binding-to-mincle-activation-of-macrophages-in%C3%A2-vitro-and-adjuvant-activity-in%C3%A2-vivo
#16
Alexandra Huber, Rie S Kallerup, Karen S Korsholm, Henrik Franzyk, Bernd Lepenies, Dennis Christensen, Camilla Foged, Roland Lang
The T-cell adjuvanticity of mycobacterial cord factor trehalose 6,6'-dimycolate (TDM) is well established. The identification of the C-type lectin Mincle on innate immune cells as the receptor for TDM and its synthetic analogue trehalose 6,6'-dibehenate (TDB) has raised interest in development of synthetic Mincle ligands as novel adjuvants. Trehalose mono- (TMXs) and diesters (TDXs) with symmetrically shortened acyl chains [denoted by X: arachidate (A), stearate (S), palmitate (P), and myristate (M)] were tested...
August 2016: Innate Immunity
https://www.readbyqxmd.com/read/27089465/mincle-mediated-translational-regulation-is-required-for-strong-nitric-oxide-production-and-inflammation-resolution
#17
Wook-Bin Lee, Ji-Seon Kang, Won Young Choi, Quanri Zhang, Chul Han Kim, Un Yung Choi, Jeongsil Kim-Ha, Young-Joon Kim
In response to persistent mycobacteria infection, the host induces a granuloma, which often fails to eradicate bacteria and results in tissue damage. Diverse host receptors are required to control the formation and resolution of granuloma, but little is known concerning their regulatory interactions. Here we show that Mincle, the inducible receptor for mycobacterial cord factor, is the key switch for the transition of macrophages from cytokine expression to high nitric oxide production. In addition to its stimulatory role on TLR-mediated transcription, Mincle enhanced the translation of key genes required for nitric oxide synthesis through p38 and eIF5A hypusination, leading to granuloma resolution...
April 18, 2016: Nature Communications
https://www.readbyqxmd.com/read/27049944/the-necrosome-promotes-pancreatic-oncogenesis-via-cxcl1-and-mincle-induced-immune-suppression
#18
Lena Seifert, Gregor Werba, Shaun Tiwari, Nancy Ngoc Giao Ly, Sara Alothman, Dalia Alqunaibit, Antonina Avanzi, Rocky Barilla, Donnele Daley, Stephanie H Greco, Alejandro Torres-Hernandez, Matthew Pergamo, Atsuo Ochi, Constantinos P Zambirinis, Mridul Pansari, Mauricio Rendon, Daniel Tippens, Mautin Hundeyin, Vishnu R Mani, Cristina Hajdu, Dannielle Engle, George Miller
Neoplastic pancreatic epithelial cells are believed to die through caspase 8-dependent apoptotic cell death, and chemotherapy is thought to promote tumour apoptosis. Conversely, cancer cells often disrupt apoptosis to survive. Another type of programmed cell death is necroptosis (programmed necrosis), but its role in pancreatic ductal adenocarcinoma (PDA) is unclear. There are many potential inducers of necroptosis in PDA, including ligation of tumour necrosis factor receptor 1 (TNFR1), CD95, TNF-related apoptosis-inducing ligand (TRAIL) receptors, Toll-like receptors, reactive oxygen species, and chemotherapeutic drugs...
April 14, 2016: Nature
https://www.readbyqxmd.com/read/27005451/signalling-through-myd88-drives-surface-expression-of-the-mycobacterial-receptors-mcl-clecsf8-clec4d-and-mincle-clec4e-following-microbial-stimulation
#19
Bernhard Kerscher, Ivy M Dambuza, Maria Christofi, Delyth M Reid, Sho Yamasaki, Janet A Willment, Gordon D Brown
The heterodimeric mycobacterial receptors, macrophage C-type lectin (MCL) and macrophage inducible C-type lectin (Mincle), are upregulated at the cell surface following microbial challenge, but the mechanisms underlying this response are unclear. Here we report that microbial stimulation triggers Mincle expression through the myeloid differentiation primary response gene 88 (MyD88) pathway; a process that does not require MCL. Conversely, we show that MCL is constitutively expressed but retained intracellularly until Mincle is induced, whereupon the receptors form heterodimers which are translocated to the cell surface...
July 2016: Microbes and Infection
https://www.readbyqxmd.com/read/26975571/isoliquiritigenin-attenuates-adipose-tissue-inflammation-in-vitro-and-adipose-tissue-fibrosis-through-inhibition-of-innate-immune-responses-in-mice
#20
Yasuharu Watanabe, Yoshinori Nagai, Hiroe Honda, Naoki Okamoto, Seiji Yamamoto, Takeru Hamashima, Yoko Ishii, Miyako Tanaka, Takayoshi Suganami, Masakiyo Sasahara, Kensuke Miyake, Kiyoshi Takatsu
Isoliquiritigenin (ILG) is a flavonoid derived from Glycyrrhiza uralensis and potently suppresses NLRP3 inflammasome activation resulting in the improvement of diet-induced adipose tissue inflammation. However, whether ILG affects other pathways besides the inflammasome in adipose tissue inflammation is unknown. We here show that ILG suppresses adipose tissue inflammation by affecting the paracrine loop containing saturated fatty acids and TNF-α by using a co-culture composed of adipocytes and macrophages...
2016: Scientific Reports
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