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https://www.readbyqxmd.com/read/29401615/differential-susceptibility-of-dectin-1-isoforms-to-functional-inactivation-by-neutrophil-and-fungal-proteases
#1
James S Griffiths, Aiysha Thompson, Matthew Stott, Ankita Benny, Natalie A Lewis, Philip R Taylor, Julian Forton, Sarah Herrick, Selinda J Orr, Eamon P McGreal
Patients with cystic fibrosis (CF) experience chronic or recurrent bacterial and fungal lung infections. Many patients with CF cannot effectively clear Aspergillus from their lungs. This may result in IgE sensitization and the development of allergic bronchopulmonary aspergillosis, or invasive infections, such as Aspergillus bronchitis. Lung disease in patients with CF is associated with neutrophil-dominated inflammation and elevated levels of the serine protease, neutrophil elastase (NE). Various C-type lectin-like receptors (CLRs), including Dectin-1 and Dectin-2, are involved in the immune response to Aspergillus...
January 22, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29400702/integrin-cd11b-negatively-regulates-mincle-induced-signaling-via-the-lyn-sirp%C3%AE-shp1-complex
#2
Quanri Zhang, Wook-Bin Lee, Ji-Seon Kang, Lark Kyun Kim, Young-Joon Kim
During mycobacteria infection, anti-inflammatory responses allow the host to avoid tissue damage caused by overactivation of the immune system; however, little is known about the negative modulators that specifically control mycobacteria-induced immune responses. Here we demonstrate that integrin CD11b is a critical negative regulator of mycobacteria cord factor-induced macrophage-inducible C-type lectin (Mincle) signaling. CD11b deficiency resulted in hyperinflammation following mycobacterial infection. Activation of Mincle by mycobacterial components turns on not only the Syk signaling pathway but also CD11b signaling and induces formation of a Mincle-CD11b signaling complex...
February 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29386115/cd209a-synergizes-with-dectin-2-and-mincle-to-drive-severe-th17-cell-mediated-schistosome-egg-induced-immunopathology
#3
Parisa Kalantari, Yoelkys Morales, Emily A Miller, Luis D Jaramillo, Holly E Ponichtera, Marcel A Wuethrich, Cheolho Cheong, Maria C Seminario, Joanne M Russo, Stephen C Bunnell, Miguel J Stadecker
The immunopathology caused by schistosome helminths varies greatly in humans and among mouse strains. A severe form of parasite egg-induced hepatic granulomatous inflammation, seen in CBA mice, is driven by Th17 cells stimulated by IL-1β and IL-23 produced by dendritic cells that express CD209a (SIGNR5), a C-type lectin receptor (CLR) related to human DC-SIGN. Here, we show that CD209a-deficient CBA mice display decreased Th17 responses and are protected from severe immunopathology. In vitro, CD209a augments the egg-induced IL-1β and IL-23 production initiated by the related CLRs Dectin-2 and Mincle...
January 30, 2018: Cell Reports
https://www.readbyqxmd.com/read/29355515/spliceosome-associated-protein-130-exacerbates-alcohol-induced-liver-injury-by-inducing-nlrp3-inflammasome-mediated-il1%C3%AE-in-mice
#4
Jong Won Kim, Yoon-Seok Roh, Hyeneui Jeong, Ho-Keun Yi, Min-Ho Lee, Chae Woong Lim, Bumseok Kim
Excessive alcohol consumption leads to chronic liver diseases. Macrophage-inducible C-type lectin (Mincle) is a C-type lectin receptor that recognizes spliceosome-associated protein 130 (SAP130) known as an endogenous ligand released from dying cells. Our aim was to examine the role of Mincle-SAP130 in the pathogenesis of alcoholic liver disease. Alcohol-induced liver injury was induced in wild-type (WT) and Mincle knout-out (KO) mice using a chronic-binge ethanol-feeding model. Mincle KO mice showed significant lower hepatic steatosis, inflammation with neutrophil infiltration, and fibrosis compared to WT mice after alcohol feeding...
January 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29290115/lipidated-brartemicin-analogues-are-potent-th1-stimulating-vaccine-adjuvants
#5
Amy J Foster, Masahiro Nagata, Xiuyuan Lu, Amy T Lynch, Zakaria Omahdi, Eri Ishikawa, Sho Yamasaki, Mattie S M Timmer, Bridget L Stocker
Effective Th1-stimulating vaccine adjuvants often engage the innate immune system via the activation of antigen presenting cells (APCs). Macrophage inducible C-type lectin (Mincle) is an activating pattern recognition receptor (PRR) expressed on the cell surface of APCs and has been identified as a potential target for Th1-stimulating adjuvants. In particular, trehalose dibehenate (TDB) is a leading Mincle-agonist and has shown much promise as an adjuvant. Herein, we report on the synthesis and adjuvanticity of rationally designed brartemicin analogues containing short, medium, and long chain lipids...
December 30, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29230225/sensing-lipids-with-mincle-structure-and-function
#6
REVIEW
Spencer J Williams
Mincle is a C-type lectin receptor that has emerged as an important player in innate immunity through its capacity to recognize a wide range of lipidic species derived from damaged/altered self and foreign microorganisms. Self-ligands include sterols (e.g., cholesterol), and β-glucosylceramides, and the protein SAP130, which is released upon cell death. Foreign lipids comprise those from both microbial pathogens and commensals and include glycerol, glucose and trehalose mycolates, and glycosyl diglycerides...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29109721/the-c-type-lectin-mincle-clues-for-a-role-in-crohn-s-disease-adjuvant-reaction
#7
Anje A Te Velde
No abstract text is available yet for this article.
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29048873/insights-into-mycobacteria-interactions-with-the-host-innate-immune-system-from-a-novel-array-of-synthetic-mycobacterial-glycans
#8
Ruixiang Blake Zheng, Sabine A F Jégouzo, Maju Joe, Yu Bai, Huu-Anh Tran, Ke Shen, Jörn Saupe, Li Xia, Md Faiaz Ahmed, Yu-Hsuan Liu, Pratap Subhashrao Patil, Ashish Tripathi, Shang-Cheng Hung, Maureen E Taylor, Todd L Lowary, Kurt Drickamer
An array of homogenous glycans representing all the major carbohydrate structures present in the cell wall of the human pathogen Mycobacterium tuberculosis and other mycobacteria has been probed with a panel of glycan-binding receptors expressed on cells of the mammalian innate immune system. The results provide an overview of interactions between mycobacterial glycans and receptors that mediate uptake and survival in macrophages, dendritic cells and sinusoidal endothelial cells. A subset of the wide variety of glycan structures present on mycobacterial surfaces interact with cells of the innate immune system through the receptors tested...
October 19, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28976590/mycobacterial-cord-factor-enhances-migration-of-neutrophil-like-hl-60-cells-by-prolonging-akt-phosphorylation
#9
Wook-Bin Lee, Ji-Jing Yan, Ji-Seon Kang, Seok Chung, Lark Kyun Kim
Trehalose 6,6'-dimycolate (TDM), or cord factor, is a crucial stimulus of immune responses during Mycobacterium tuberculosis infection. Although TDM has immuno-stimulatory properties, including adjuvant activity and the ability to induce granuloma formation, the mechanisms underlying these remain unknown. We hypothesized that TDM stimulates transendothelial migration of neutrophils, which are the first immune cells to infiltrate the tissue upon infection. In this study, it was shown that TDM enhances N-formylmethionyl-leucyl-phenylalanine (fMLP)-induced chemotaxis and transendothelial movement by prolonging AKT phosphorylation in human neutrophils...
October 4, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28888778/mincle-inhibits-neutrophils-and-macrophages-apoptosis-in-a-fumigatus-keratitis
#10
Jing Lin, Kun He, Guiqiu Zhao, Cui Li, Liting Hu, Guoqiang Zhu, Yawen Niu, Guipei Hao
PURPOSE: To determine whether macrophage inducible C-type lectin (Mincle) regulates neutrophils and macrophages apoptosis in A. fumigatus keratitis. MATERIALS AND METHODS: A murine model (C57BL/6) of fungal keratitis (AF) was established by gently scraping corneal central epithelium, smearing A. fumigatus on the epithelium surface and covering the eye with contact lenses. AF cell model was established by extracting neutrophils (PMN) and macrophages, and then infecting cells with A...
November 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28791019/macrophage-inducible-c-type-lectin-as-a-multifunctional-player-in-immunity
#11
REVIEW
Emmanuel C Patin, Selinda Jane Orr, Ulrich E Schaible
The macrophage-inducible C-type lectin (Mincle) is an innate immune receptor on myeloid cells sensing diverse entities including pathogens and damaged cells. Mincle was first described as a receptor for the mycobacterial cell wall glycolipid, trehalose-6,6'-dimycolate, or cord factor, and the mammalian necrotic cell-derived alarmin histone deacetylase complex unit Sin3-associated protein 130. Upon engagement by its ligands, Mincle induces secretion of innate cytokines and other immune mediators modulating inflammation and immunity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28763100/fungal-derived-cues-promote-ocular-autoimmunity-through-a-dectin-2-card9-mediated-mechanism
#12
B R Brown, E J Lee, P E Snow, E E Vance, Y Iwakura, N Ohno, N Miura, X Lin, G D Brown, C A Wells, J R Smith, R R Caspi, H L Rosenzweig
Uveitis (intraocular inflammation) is a leading cause of loss of vision. Although its aetiology is largely speculative, it is thought to arise from complex genetic-environmental interactions that break immune tolerance to generate eye-specific autoreactive T cells. Experimental autoimmune uveitis (EAU), induced by immunization with the ocular antigen, interphotoreceptor retinoid binding protein (IRBP), in combination with mycobacteria-containing complete Freund's adjuvant (CFA), has many clinical and histopathological features of human posterior uveitis...
December 2017: Clinical and Experimental Immunology
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
#13
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
#14
REVIEW
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 against 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 immunereceptor 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-κB) through Syk- and CARD9-dependent pathway...
2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28483856/toll-like-receptor-2-and-mincle-cooperatively-sense-corynebacterial-cell-wall-glycolipids
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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