Read by QxMD icon Read


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
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
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 5, 2016: Immunity
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
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 (ALD). However, the mechanisms by which TLR-dependent inflammatory responses and alcohol-induced hepatocellular damage coordinately lead to ALD are not completely understood. In this study, we found that mice deficient in IRAKM, a proximal Toll-like receptor pathway molecule typically associated with inhibition of TLR signaling, were actually protected from chronic ethanol-induced liver injury...
September 15, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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
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
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
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
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
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
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...
2016: Nature Communications
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
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
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
Emmanuel C Patin, Sam Willcocks, Selinda Orr, Theresa H Ward, Roland Lang, Ulrich E Schaible
The role of macrophage-inducible C-type lectin (Mincle) in anti-inflammatory responses has not yet been fully characterized. Herein, we show that engagement of Mincle by trehalose-dimycolate or mycobacteria promotes IL-10 production in macrophages, which causes down-regulation of IL-12p40 secretion. Thus, Mincle mediates both pro- as well as anti-inflammatory responses.
April 2016: Innate Immunity
Ellen J Lee, Brieanna R Brown, Emily E Vance, Paige E Snow, Phyllis B Silver, David Heinrichs, Xin Lin, Yoichiro Iwakura, Christine A Wells, Rachel R Caspi, Holly L Rosenzweig
Uveitis, which occurs in association with systemic immunological diseases, presents a considerable medical challenge because of incomplete understanding of its pathogenesis. The signals that initiate T cells to target the eye, which may be of infectious or noninfectious origin, are poorly understood. Experimental autoimmune uveoretinitis (EAU) develops in mice immunized with the endogenous retinal protein interphotoreceptor retinoid binding protein in the presence of the adjuvant CFA. EAU manifests as posterior ocular inflammation consisting of vasculitis, granulomas, retinal damage, and invasion of self-reactive T cells, which are key clinical features of human uveitis...
April 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Stephanie H Greco, Syed Kashif Mahmood, Anne-Kristin Vahle, Atsuo Ochi, Jennifer Batel, Michael Deutsch, Rocky Barilla, Lena Seifert, H Leon Pachter, Donnele Daley, Alejandro Torres-Hernandez, Mautin Hundeyin, Vishnu R Mani, George Miller
Regulation of Toll-like receptor responses is critical for limiting tissue injury and autoimmunity in both sepsis and sterile inflammation. We found that Mincle, a C-type lectin receptor, regulates proinflammatory Toll-like receptor 4 signaling. Specifically, Mincle ligation diminishes Toll-like receptor 4-mediated inflammation, whereas Mincle deletion or knockdown results in marked hyperresponsiveness to lipopolysaccharide in vitro, as well as overwhelming lipopolysaccharide-mediated inflammation in vivo. Mechanistically, Mincle deletion does not up-regulate Toll-like receptor 4 expression or reduce interleukin 10 production after Toll-like receptor 4 ligation; however, Mincle deletion decreases production of the p38 mitogen-activated protein kinase-dependent inhibitory intermediate suppressor of cytokine signaling 1, A20, and ABIN3 and increases expression of the Toll-like receptor 4 coreceptor CD14...
July 2016: Journal of Leukocyte Biology
Dylan G M Smith, Spencer J Williams
Microbes produce a wide range of small molecule glycoconjugates that constitute unique molecular signatures. These molecules are recognized by a range of detection systems, triggering immune responses to microbial pathogens and commensals. The antigen-presenting molecules of the CD1 class, CD1a-d, capture lipidic molecules and present them to diverse and innate-like T cell populations including natural killer T cells and germline-encoded mycolyl reactive T cells. The antigen-presenting molecule MR1 captures vitamin B metabolites and presents them to mucosal associated invariant T cells...
February 2016: Carbohydrate Research
Zhijun Zhang, Long He, Shuang Hu, Yi Wang, Qiaohong Lai, Ping Yang, Qilin Yu, Shu Zhang, Fei Xiong, Sakine Simsekyilmaz, Qin Ning, Jinxiu Li, Dongshan Zhang, Hongliang Zhang, Xudong Xiang, Zhiguang Zhou, Hui Sun, Cong-Yi Wang
Previously, we demonstrated that Agrocybe aegerita lectin (AAL), a galectin isolated from edible mushroom Agrocybe aegerita, exerts potent anti-tumor activity, while the mechanisms by which AAL suppresses tumor growth are yet to be elucidated. Here, we conducted studies with focus for its impact on the cecal ligation and puncture (CLP)-induced innate immune response. Administration of AAL significantly exacerbated the severity of CLP-induced septic shock as manifested the increased lethality. AAL promoted inflammatory cytokine production by preferentially regulating macrophage activation and recruitment...
2015: American Journal of Translational Research
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"