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https://www.readbyqxmd.com/read/28722316/the-mincle-ligand-trehalose-dibehenate-differentially-modulates-m1-like-and-m2-like-macrophage-phenotype-and-function-via-syk-signaling
#1
Kristel Kodar, Jacquie L Harper, Melanie J McConnell, Mattie S M Timmer, Bridget L Stocker
INTRODUCTION: Macrophages play a significant role in the progression of diseases, such as cancer, making them a target for immune-modulating agents. Trehalose dibehenate (TDB) is known to activate M1-like macrophages via Mincle, however, the effect of TDB on M2-like macrophages, which are found in the tumor microenvironment, has not been studied. METHODS: qRT-PCR, flow cytometry, cytokine ELISA, and Western Blotting were used to study the effect of TDB on GM-CSF and M-CSF/IL-4 derived bone marrow macrophages (BMMs) from C57BL/6 and Mincle(-/-) mice...
July 19, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28494724/c-type-lectin-receptor-old-friend-and-new-player
#2
Hai Hou, Yahui Guo, Qing Chang, Tianming Luo, Xin Wu, Xueqiang Zhao
During the last two decades, C-type lectin receptors (CLRs) have been demonstrated to play key roles in initiating the host immune response upon fungal infection. It is well established that CLRs, such as Dectin-1, Dectin-2, Dectin-3 and Mincle, recognize the cell wall component from the infected microorganisms by using their carbohydrate recognition domain (CRD). Upon stimulation, CLRs induce multiple signal transduction cascades through their own immune-receptor tyrosine-based activation motifs (ITAMs) or interacting with ITAM-containing adaptor proteins such as FcRγ, which then lead to the activation of nuclear factor kappa B (NF-kB) through Syk- and CARD9-dependent pathway...
May 9, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28483856/toll-like-receptor-2-and-mincle-cooperatively-sense-corynebacterial-cell-wall-glycolipids
#3
Judith Schick, Philipp Etschel, Rebeca Bailo, Lisa Ott, Apoorva Bhatt, Bernd Lepenies, Carsten Kirschning, Andreas Burkovski, Roland Lang
Nontoxigenic Corynebacterium diphtheriae and Corynebacterium ulcerans cause invasive disease in humans and animals. Host sensing of corynebacteria is largely uncharacterized, albeit the recognition of lipoglycans by Toll-like receptor 2 (TLR2) appears to be important for macrophage activation by corynebacteria. The members of the order Corynebacterineae (e.g., mycobacteria, nocardia, and rhodococci) share a glycolipid-rich cell wall dominated by mycolic acids (termed corynomycolic acids in corynebacteria). The mycolic acid-containing cord factor of mycobacteria, trehalose dimycolate, activates the C-type lectin receptor (CLR) Mincle...
July 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28440726/expression-of-c-type-lectin-receptor-mrna-in-chronic-otitis-media-with-cholesteatoma
#4
Sang Hoon Kim, Seung-Ho Han, Jae Yong Byun, Moon Suh Park, Young Il Kim, Seung Geun Yeo
CONCLUSIONS: The levels of expression of various C-type lectin receptors (CLRs) messenger ribo nucleic acids (mRNAs) were significantly higher in cholesteatomas than in normal skin, suggesting that these CLRs may be involved in the pathogenesis of cholesteatoma. OBJECTIVES: Altered expression of pattern recognition receptors may be associated with immune responses in patients with cholesteatoma. This study assessed the levels of expression of CLR mRNAs in normal skin and in cholesteatoma...
June 2017: Acta Oto-laryngologica
https://www.readbyqxmd.com/read/28393919/association-of-c-type-lectin-mincle-with-fc%C3%AE%C2%B5ri%C3%AE-%C3%AE-subunits-leads-to-functional-activation-of-rbl-2h3-cells-through-syk
#5
Chisato Honjoh, Kazuyasu Chihara, Hatsumi Yoshiki, Shota Yamauchi, Kenji Takeuchi, Yuji Kato, Yukio Hida, Tamotsu Ishizuka, Kiyonao Sada
Macrophage-inducible C-type lectin (Mincle) interacts with the γ-subunit of high-affinity IgE receptor (FcεRIγ) and activates Syk by recognizing its specific ligand, trehalose-6,6'-dimycolate, a glycolipid produced by Mycobacterium tuberculosis. It has been suggested that mast cells participate in the immune defense against pathogenic microbes including M. tuberculosis, although the functions are still uncertain. In this study, we examined the Mincle-mediated signaling pathway and cellular responses using RBL-2H3 cells...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28384255/trehalose-dimycolate-interferes-with-fc%C3%AE-r-mediated-phagosome-maturation-through-mincle-shp-1-and-fc%C3%AE-riib-signalling
#6
Emmanuel C Patin, Anna C Geffken, Sam Willcocks, Christoph Leschczyk, Albert Haas, Falk Nimmerjahn, Roland Lang, Theresa H Ward, Ulrich E Schaible
The causative agent of tuberculosis, Mycobacterium tuberculosis (M. tuberculosis), contains an abundant cell wall glycolipid and a crucial virulence factor, trehalose-6,6'-dimycolate (TDM). TDM causes delay of phagosome maturation and thus promotes survival of mycobacteria inside host macrophages by a not fully understood mechanism. TDM signals through the Monocyte-INducible C-type LEctin (Mincle), a recently identified pattern recognition receptor. Here we show that recruitment of Mincle by TDM coupled to immunoglobulin (Ig)G-opsonised beads during Fcγ receptor (FcγR)-mediated phagocytosis interferes with phagosome maturation...
2017: PloS One
https://www.readbyqxmd.com/read/28373578/intracellular-metabolite-%C3%AE-glucosylceramide-is-an-endogenous-mincle-ligand-possessing-immunostimulatory-activity
#7
Masahiro Nagata, Yoshihiro Izumi, Eri Ishikawa, Ryoko Kiyotake, Rieko Doi, Satoru Iwai, Zakaria Omahdi, Toshiyuki Yamaji, Tomofumi Miyamoto, Takeshi Bamba, Sho Yamasaki
Sensing and reacting to tissue damage is a fundamental function of immune systems. Macrophage inducible C-type lectin (Mincle) is an activating C-type lectin receptor that senses damaged cells. Notably, Mincle also recognizes glycolipid ligands on pathogens. To elucidate endogenous glycolipids ligands derived from damaged cells, we fractionated supernatants from damaged cells and identified a lipophilic component that activates reporter cells expressing Mincle. Mass spectrometry and NMR spectroscopy identified the component structure as β-glucosylceramide (GlcCer), which is a ubiquitous intracellular metabolite...
April 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28298521/the-interaction-of-pneumocystis-with-the-c-type-lectin-receptor-mincle-exerts-a-significant-role-in-host-defense-against-infection
#8
Theodore J Kottom, Deanne M Hebrink, Paige E Jenson, Vijayalakshmi Nandakumar, Marcel Wüthrich, Huafeng Wang, Bruce Klein, Sho Yamasaki, Bernd Lepenies, Andrew H Limper
Pneumocystis pneumonia (PCP) remains a major cause of morbidity and mortality within immunocompromised patients. In this study, we examined the potential role of macrophage-inducible C-type lectin (Mincle) for host defense against Pneumocystis Binding assays implementing soluble Mincle carbohydrate recognition domain fusion proteins demonstrated binding to intact Pneumocystis carinii as well as to organism homogenates, and they purified major surface glycoprotein/glycoprotein A derived from the organism. Additional experiments showed that rats with PCP expressed increased Mincle mRNA levels...
May 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28292894/receptor-mincle-promotes-skin-allergies-and-is-capable-of-recognizing-cholesterol-sulfate
#9
Alexey V Kostarnoy, Petya G Gancheva, Bernd Lepenies, Amir I Tukhvatulin, Alina S Dzharullaeva, Nikita B Polyakov, Daniil A Grumov, Daria A Egorova, Andrey Y Kulibin, Maxim A Bobrov, Ekaterina A Malolina, Pavel A Zykin, Andrey I Soloviev, Evgeniy Riabenko, Diana V Maltseva, Dmitry A Sakharov, Alexander G Tonevitsky, Lyudmila V Verkhovskaya, Denis Y Logunov, Boris S Naroditsky, Alexander L Gintsburg
Sterile (noninfected) inflammation underlies the pathogenesis of many widespread diseases, such as allergies and autoimmune diseases. The evolutionarily conserved innate immune system is considered to play a key role in tissue injury recognition and the subsequent development of sterile inflammation; however, the underlying molecular mechanisms are not yet completely understood. Here, we show that cholesterol sulfate, a molecule present in relatively high concentrations in the epithelial layer of barrier tissues, is selectively recognized by Mincle (Clec4e), a C-type lectin receptor of the innate immune system that is strongly up-regulated in response to skin damage...
March 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28282442/characterization-of-c-type-lectins-reveals-an-unexpectedly-limited-interaction-between-cryptococcus-neoformans-spores-and-dectin-1
#10
Naomi M Walsh, Marcel Wuthrich, Huafeng Wang, Bruce Klein, Christina M Hull
Phagocytosis by innate immune cells is an important process for protection against multiple pathologies and is particularly important for resistance to infection. However, phagocytosis has also been implicated in the progression of some diseases, including the dissemination of the human fungal pathogen, Cryptococcus neoformans. Previously, we identified Dectin-1 as a likely phagocytic receptor for C. neoformans spores through the use of soluble components in receptor-ligand blocking experiments. In this study, we used gain-of-function and loss-of-function assays with intact cells to evaluate the in vivo role of Dectin-1 and other C-type lectins in interactions with C...
2017: PloS One
https://www.readbyqxmd.com/read/28264048/macrophage-inducible-c-type-lectin-mincle-recognizes-glycosylated-surface-s-layer-of-the-periodontal-pathogen-tannerella-forsythia
#11
Sreedevi Chinthamani, Rajendra P Settem, Kiyonobu Honma, Jason G Kay, Ashu Sharma
The oral pathogen Tannerella forsythia is implicated in the development of periodontitis, a common inflammatory disease that leads to the destruction of the gum and tooth supporting tissues, often leading to tooth loss. T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. The T. forsythia S-layer has been implicated in the modulation of cytokine responses of antigen presenting cells, such as macrophages, that play a significant role during inflammation associated with periodontitis...
2017: PloS One
https://www.readbyqxmd.com/read/28223515/rational-design-of-adjuvants-targeting-the-c-type-lectin-mincle
#12
Alexiane Decout, Sandro Silva-Gomes, Daniel Drocourt, Sophie Barbe, Isabelle André, Francisco J Cueto, Thierry Lioux, David Sancho, Eric Pérouzel, Alain Vercellone, Jacques Prandi, Martine Gilleron, Gérard Tiraby, Jérôme Nigou
The advances in subunit vaccines development have intensified the search for potent adjuvants, particularly adjuvants inducing cell-mediated immune responses. Identification of the C-type lectin Mincle as one of the receptors underlying the remarkable immunogenicity of the mycobacterial cell wall, via recognition of trehalose-6,6'-dimycolate (TDM), has opened avenues for the rational design of such molecules. Using a combination of chemical synthesis, biological evaluation, molecular dynamics simulations, and protein mutagenesis, we gained insight into the molecular bases of glycolipid recognition by Mincle...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28202166/m1-macrophage-triggered-by-mincle-leads-to-a-deterioration-of-acute-kidney-injury
#13
Tsuyoshi Inoue
In the early stage of acute kidney injury, M1 macrophages are proinflammatory and destructive. In this study, Lv et al. reveal that Mincle (macrophage-inducible C-type lectin, Clec4e) is expressed on M1 macrophages in acute kidney injury, and the kidney is protected in a murine model of cisplatin-induced renal injury by inhibiting Mincle expression on macrophages. Mincle expression is regulated by Toll-like receptor 4/nuclear factor κB signaling, and Mincle maintains the inflammatory phenotype through spleen tyrosine kinase signaling, leading to acute kidney injury...
March 2017: Kidney International
https://www.readbyqxmd.com/read/28186242/mincle-mediated-neutrophil-extracellular-trap-formation-by-regulation-of-autophagy
#14
Atul Sharma, Tanner J Simonson, Christopher N Jondle, Bibhuti B Mishra, Jyotika Sharma
Background: Neutrophil extracellular traps (NETs) constitute antimicrobial function of neutrophils but have also been linked to perpetuation of inflammation. Despite this evident physiological relevance, mechanistic understanding of NET formation is poor. In this study, we examined the mechanism by which Mincle, a C-type lectin receptor, regulates NET formation. Methods: NET formation, reactive oxygen species, autophagy activation and intracellular signaling pathways were analyzed in Mincle-sufficient and -deficient neutrophils stimulated in vitro with various stimuli and in vivo during Klebsiella infection...
April 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28141595/the-role-of-mincle-in-innate-immune-to-fungal-keratitis
#15
Guiqiu Zhao, Qiang Xu, Jing Lin, Wenjun Chen, Tingting Cui, Liting Hu, Nan Jiang
INTRODUCTION: This study aimed to detect the early expression of macrophage-inducible C-type lectin (Mincle) and investigate its role in the innate immune response of fungal keratitis (FK). METHODOLOGY: Wistar rats were used to make fungal keratitis models. The inflammatory responses and corneal lesions were observed by slit-lamp microscope.RT-PCR, immunohistochemistry, and immunofluorescence were used to detect the expression of Mincle in the rat corneal epithelium...
January 30, 2017: Journal of Infection in Developing Countries
https://www.readbyqxmd.com/read/28112221/mincle-activation-enhances-neutrophil-migration-and-resistance-to-polymicrobial-septic-peritonitis
#16
Wook-Bin Lee, Ji-Jing Yan, Ji-Seon Kang, Quanri Zhang, Won Young Choi, Lark Kyun Kim, Young-Joon Kim
Sepsis is a systemic inflammatory response to bacterial infection. The therapeutic options for treating sepsis are limited. Impaired neutrophil recruitment into the infection site is directly associated with severe sepsis, but the precise mechanism is unclear. Here, we show that Mincle plays a key role in neutrophil migration and resistance during polymicrobial sepsis. Mincle-deficient mice exhibited lower survival rates in experimental sepsis from cecal ligation and puncture and Escherichia coli-induced peritonitis...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28095348/immune-transcriptome-reveals-the-mincle-c-type-lectin-receptor-acts-as-a-partial-replacement-for-tlr4-in-lipopolysaccharide-mediated-inflammatory-response-in-barramundi-lates-calcarifer
#17
Emmanuelle Zoccola, Stuart Kellie, Andrew C Barnes
Fish represent the most diverse and abundant extant vertebrate infraclass. They are also one of the earliest divergent phyla with adaptive immunity based on antigen recognition by MHC and immunoglobulin. The aquaculture industry, which currently provides more than half of the fish for human consumption globally, has successfully exploited the adaptive immune system of fish through mass vaccination programs. However, vaccination against highly diverse antigens, mostly carbohydrates, such as capsular polysaccharides and lipopolysaccharide (LPS) is challenging...
March 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28017324/the-pattern-recognition-receptor-mincle-is-essential-for-maintaining-the-m1-macrophage-phenotype-in-acute-renal-inflammation
#18
Lin L Lv, Patrick Ming-Kuen Tang, Chun J Li, Yong K You, Jinhong Li, Xiao-Ru Huang, Jun Ni, Min Feng, Bi C Liu, Hui-Yao Lan
Mincle (macrophage-inducible C-type lectin, Clec4e) is a transmembrane pattern recognition receptor involving the innate immunity, but its role in kidney disease is still unexplored. In the obstructed kidney of the unilateral ureteral obstruction model of renal injury, Mincle was specifically detected in the infiltrating M1 macrophages (CD68(+)iNOS(+) cells) on day one but was rapidly reduced following reduction of M1 macrophages during the progression of kidney injury. Interestingly, Mincle-expressing macrophages were progressively increased in the cisplatin-induced acute kidney injury model, where iNOS expression was detected in the CD68(+) cells following Mincle induction...
December 22, 2016: Kidney International
https://www.readbyqxmd.com/read/27999992/c-type-lectins-their-network-and-roles-in-pathogen-recognition-and-immunity
#19
REVIEW
Sabine Mayer, Marie-Kristin Raulf, Bernd Lepenies
C-type lectins (CTLs) represent the most complex family of animal/human lectins that comprises 17 different groups. During evolution, CTLs have developed by diversification to cover a broad range of glycan ligands. However, ligand binding by CTLs is not necessarily restricted to glycans as some CTLs also bind to proteins, lipids, inorganic molecules, or ice crystals. CTLs share a common fold that harbors a Ca(2+) for contact to the sugar and about 18 invariant residues in a phylogenetically conserved pattern...
February 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/27988097/parasites-dampen-dendritic-cell-activation-to-ensure-their-survival
#20
Esther von Stebut
Dendritic cells (DCs) are critical for induction of protective immunity against Leishmania major. However, DC activation occurs only several weeks after parasite transmission. Parasites synthesize a macrophage-inducible C-type lectin (Mincle) ligand. Engagement of Mincle by the parasite ligand dampens DC activation, thus delaying induction of interferon-γ-producing T cells responsible for parasite eradication.
February 2017: Trends in Parasitology
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