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Dectin-2

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https://www.readbyqxmd.com/read/27872290/the-innate-immune-receptor-dectin-2-mediates-the-phagocytosis-of-cancer-cells-by-kupffer-cells-for-the-suppression-of-liver-metastasis
#1
Yoshitaka Kimura, Asuka Inoue, Sho Hangai, Shinobu Saijo, Hideo Negishi, Junko Nishio, Sho Yamasaki, Yoichiro Iwakura, Hideyuki Yanai, Tadatsugu Taniguchi
Tumor metastasis is the cause of most cancer deaths. Although metastases can form in multiple end organs, the liver is recognized as a highly permissive organ. Nevertheless, there is evidence for immune cell-mediated mechanisms that function to suppress liver metastasis by certain tumors, although the underlying mechanisms for the suppression of metastasis remain elusive. Here, we show that Dectin-2, a C-type lectin receptor (CLR) family of innate receptors, is critical for the suppression of liver metastasis of cancer cells...
November 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
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
#2
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
#3
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/27432944/e3-ubiquitin-ligase-cbl-b-negatively-regulates-c-type-lectin-receptor-mediated-antifungal-innate-immunity
#4
Le-Le Zhu, Tian-Ming Luo, Xia Xu, Ya-Hui Guo, Xue-Qiang Zhao, Ting-Ting Wang, Bing Tang, Yuan-Ying Jiang, Jin-Fu Xu, Xin Lin, Xin-Ming Jia
Activation of various C-type lectin receptors (CLRs) initiates potent proinflammatory responses against various microbial infections. However, how activated CLRs are negatively regulated remains unknown. In this study, we report that activation of CLRs Dectin-2 and Dectin-3 by fungi infections triggers them for ubiquitination and degradation in a Syk-dependent manner. Furthermore, we found that E3 ubiquitin ligase Casitas B-lineage lymphoma protein b (Cbl-b) mediates the ubiquitination of these activated CLRs through associating with each other via adapter protein FcR-γ and tyrosine kinase Syk, and then the ubiquitinated CLRs are sorted into lysosomes for degradation by an endosomal sorting complex required for transport (ESCRT) system...
July 25, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27428901/inhibition-of-cblb-protects-from-lethal-candida-albicans-sepsis
#5
Gerald Wirnsberger, Florian Zwolanek, Tomoko Asaoka, Ivona Kozieradzki, Luigi Tortola, Reiner A Wimmer, Anoop Kavirayani, Friedrich Fresser, Gottfried Baier, Wallace Y Langdon, Fumiyo Ikeda, Karl Kuchler, Josef M Penninger
Fungal infections claim an estimated 1.5 million lives each year. Mechanisms that protect from fungal infections are still elusive. Recognition of fungal pathogens relies on C-type lectin receptors (CLRs) and their downstream signaling kinase SYK. Here we report that the E3 ubiquitin ligase CBLB controls proximal CLR signaling in macrophages and dendritic cells. We show that CBLB associates with SYK and ubiquitinates SYK, dectin-1, and dectin-2 after fungal recognition. Functionally, CBLB deficiency results in increased inflammasome activation, enhanced reactive oxygen species production, and increased fungal killing...
August 2016: Nature Medicine
https://www.readbyqxmd.com/read/27428899/targeting-cblb-as-a-potential-therapeutic-approach-for-disseminated-candidiasis
#6
Yun Xiao, Juan Tang, Hui Guo, Yixia Zhao, Rong Tang, Song Ouyang, Qiuming Zeng, Chad A Rappleye, Murugesan V S Rajaram, Larry S Schlesinger, Lijian Tao, Gordon D Brown, Wallace Y Langdon, Belinda T Li, Jian Zhang
Disseminated candidiasis has become one of the leading causes of hospital-acquired blood stream infections with high mobility and mortality. However, the molecular basis of host defense against disseminated candidiasis remains elusive, and treatment options are limited. Here we report that the E3 ubiquitin ligase CBLB directs polyubiquitination of dectin-1 and dectin-2, two key pattern-recognition receptors for sensing Candida albicans, and their downstream kinase SYK, thus inhibiting dectin-1- and dectin-2-mediated innate immune responses...
August 2016: Nature Medicine
https://www.readbyqxmd.com/read/27358401/dectin-2-recognizes-mannosylated-o-antigens-of-human-opportunistic-pathogens-and-augments-lipopolysaccharide-activation-of-myeloid-cells
#7
Alexandra Wittmann, Dimitra Lamprinaki, Kristian M Bowles, Ewa Katzenellenbogen, Yuriy A Knirel, Chris Whitfield, Takashi Nishimura, Naoki Matsumoto, Kazuo Yamamoto, Yoichiro Iwakura, Shinobu Saijo, Norihito Kawasaki
LPS consists of a relatively conserved region of lipid A and core oligosaccharide and a highly variable region of O-antigen polysaccharide. Whereas lipid A is known to bind to the Toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex, the role of the O-antigen remains unclear. Here we report a novel molecular interaction between dendritic cell-associated C-type lectin-2 (Dectin-2) and mannosylated O-antigen found in a human opportunistic pathogen, Hafnia alvei PCM 1223, which has a repeating unit of [-Man-α1,3-Man-α1,2-Man-α1,2-Man-α1,2-Man-α1,3-]...
August 19, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27354239/c-type-lectin-receptor-expression-on-human-basophils-and-effects-of-allergen-specific-immunotherapy
#8
K Lundberg, F Rydnert, S Broos, M Andersson, L Greiff, M Lindstedt
Basophils are emerging as immunoregulatory cells capable of interacting with their environment not only via their characteristic IgE-mediated activation, but also in an IgE-independent manner. Basophils are known to express and respond to stimulation via TLR2, TLR4, DC-SIGN and DCIR, but whether basophils also express other C-type lectin receptors (CLRs) is largely unknown. In this study, we investigate the CLR expression profile of human basophils using multicolour flow cytometry. As FcRs as well as some CLRs are associated with allergen recognition and shown to be involved in subsequent immune responses, the expression of CLRs and FcRs on peripheral blood basophils, as well as their frequency, was monitored for 1 year in subjects undergoing subcutaneous allergen-specific immunotherapy (AIT)...
September 2016: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/27194783/phosphoinositide-3-kinase-%C3%AE-regulates-dectin-2-signaling-and-the-generation-of-th2-and-th17-immunity
#9
Min Jung Lee, Eri Yoshimoto, Shinobu Saijo, Yoichiro Iwakura, Xin Lin, Howard R Katz, Yoshihide Kanaoka, Nora A Barrett
The C-type lectin receptor Dectin-2 can trigger the leukotriene C4 synthase-dependent generation of cysteinyl leukotrienes and the caspase-associated recruitment domain 9- and NF-κB-dependent generation of cytokines, such as IL-23, IL-6, and TNF-α, to promote Th2 and Th17 immunity, respectively. Dectin-2 activation also elicits the type 2 cytokine IL-33, but the mechanism by which Dectin-2 induces these diverse innate mediators is poorly understood. In this study, we identify a common upstream requirement for PI3Kδ activity for the generation of each Dectin-2-dependent mediator elicited by the house dust mite species, Dermatophagoides farinae, using both pharmacologic inhibition and small interfering RNA knockdown of PI3Kδ in bone marrow-derived dendritic cells...
July 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27189427/dectin-1-and-dectin-2-promote-control-of-the-fungal-pathogen-trichophyton-rubrum-independently-of-il-17-and-adaptive-immunity-in-experimental-deep-dermatophytosis
#10
Fabio Sy Yoshikawa, Rikio Yabe, Yoichiro Iwakura, Sandro R de Almeida, Shinobu Saijo
Dermatophytoses are chronic fungal infections, the main causative agent of which is Trichophyton rubrum (T. rubrum). Despite their high occurrence worldwide, the immunological mechanisms underlying these diseases remain largely unknown. Here, we uncovered the C-type lectin receptors, Dectin-1 and Dectin-2, as key elements in the immune response to T. rubrum infection in a model of deep dermatophytosis. In vitro, we observed that deficiency in Dectin-1 and Dectin-2 severely compromised cytokine production by dendritic cells...
July 2016: Innate Immunity
https://www.readbyqxmd.com/read/27092298/mechanistic-insights-into-the-role-of-c-type-lectin-receptor-card9-signaling-in-human-antifungal-immunity
#11
REVIEW
Rebecca A Drummond, Michail S Lionakis
Human CARD9 deficiency is an autosomal recessive primary immunodeficiency disorder caused by biallelic mutations in the gene CARD9, which encodes a signaling protein that is found downstream of many C-type lectin receptors (CLRs). CLRs encompass a large family of innate recognition receptors, expressed predominantly by myeloid and epithelial cells, which bind fungal carbohydrates and initiate antifungal immune responses. Accordingly, human CARD9 deficiency is associated with the spontaneous development of persistent and severe fungal infections that primarily localize to the skin and subcutaneous tissue, mucosal surfaces and/or central nervous system (CNS)...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27046240/the-role-of-dectin-2-for-host-defense-against-disseminated-candidiasis
#12
Daniela C Ifrim, Jessica Quintin, Flavie Courjol, Ineke Verschueren, J Han van Krieken, Frank Koentgen, Chantal Fradin, Neil A R Gow, Leo A B Joosten, Jos W M van der Meer, Frank van de Veerdonk, Mihai G Netea
Despite the fact that Candida albicans is an important human fungal pathogen and Dectin-2 is a major pattern recognition receptor for fungi, our knowledge regarding the role of Dectin-2 for the host defense against disseminated candidiasis is limited. Dectin-2 deficient (Dectin-2(-/-)) mice were more susceptible to systemic candidiasis, and the susceptibility was mirrored by an elevated fungal load in the kidneys that correlated with the presence of large inflammatory foci. Phagocytosis of Candida by the macrophages lacking the Dectin-2 receptor was moderately decreased, while production of most of the macrophage-derived cytokines from Dectin-2(-/-) mice with systemic candidiasis was decreased...
April 2016: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/27004978/glycobiology-simplified-diverse-roles-of-glycan-recognition-in-inflammation
#13
REVIEW
Ronald L Schnaar
Glycans and complementary glycan-binding proteins are essential components in the language of cell-cell interactions in immunity. The study of glycan function is the purview of glycobiology, which has often been presented as an unusually complex discipline. In fact, the human glycome, composed of all of its glycans, is built primarily from only 9 building blocks that are combined by enzymes (writers) with specific and limited biosynthetic capabilities into a tractable and increasingly accessible number of potential glycan patterns that are functionally read by several dozen human glycan-binding proteins (readers)...
June 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/26921309/mincle-activation-and-the-syk-card9-signaling-axis-are-central-to-the-development-of-autoimmune-disease-of-the-eye
#14
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
https://www.readbyqxmd.com/read/26863539/allergen-specific-immunotherapy-alters-the-frequency-as-well-as-the-fcr-and-clr-expression-profiles-of-human-dendritic-cell-subsets
#15
Kristina Lundberg, Frida Rydnert, Sissela Broos, Morgan Andersson, Lennart Greiff, Malin Lindstedt
Allergen-specific immunotherapy (AIT) induces tolerance and shifts the Th2 response towards a regulatory T-cell profile. The underlying mechanisms are not fully understood, but dendritic cells (DC) play a vital role as key regulators of T-cell responses. DCs interact with allergens via Fc receptors (FcRs) and via certain C-type lectin receptors (CLRs), including CD209/DC-SIGN, CD206/MR and Dectin-2/CLEC6A. In this study, the effect of AIT on the frequencies as well as the FcR and CLR expression profiles of human DC subsets was assessed...
2016: PloS One
https://www.readbyqxmd.com/read/26644324/a-critical-role-of-dectin-1-in-hypersensitivity-pneumonitis
#16
Mari Higashino-Kameda, Toshiki Yabe-Wada, Shintaro Matsuba, Kazuya Takeda, Kazushi Anzawa, Takashi Mochizuki, Koichi Makimura, Shinobu Saijo, Yoichiro Iwakura, Hirohisa Toga, Akira Nakamura
OBJECTIVES AND DESIGN: Hypersensitivity pneumonitis (HP) is a pulmonary disease caused by repeated exposure to various aspiration antigens, including bacteria and fungi. Although TLRs are known to be required for the generation of HP triggered by bacteria, the significance of fungal receptors remains unclear. The present study aimed to investigate whether Dectin-1 and Dectin-2 contribute to the development of experimental HP triggered by the fungus Trichosporon asahii (T. asahii) that causes summer-type HP...
March 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/26558717/mycobacterial-receptor-clec4d-clecsf8-mcl-is-coregulated-with-mincle-and-upregulated-on-mouse-myeloid-cells-following-microbial-challenge
#17
Bernhard Kerscher, Gillian J Wilson, Delyth M Reid, Daiki Mori, Julie A Taylor, Gurdyal S Besra, Sho Yamasaki, Janet A Willment, Gordon D Brown
The C-type lectin receptor (CTLR), Clec4d (MCL, CLECSF8), is a member of the Dectin-2 cluster of CTLRs, which also includes the related receptors Mincle and Dectin-2. Like Mincle, Clec4d recognizes mycobacterial cord factor, trehalose dimycolate, and we recently demonstrated its key role in anti-mycobacterial immunity in mouse and man. Here, we characterized receptor expression in naïve mice, under inflammatory conditions, and during Mycobacterium bovis BCG infection using newly generated monoclonal antibodies...
February 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/26385440/the-schistosoma-mansoni-t2-ribonuclease-omega-1-modulates-inflammasome-dependent-il-1%C3%AE-secretion-in-macrophages
#18
Brian J Ferguson, Stephen A Newland, Sarah E Gibbs, Panagiotis Tourlomousis, Paula Fernandes dos Santos, Meghana N Patel, Samuel W Hall, Henning Walczak, Gabriele Schramm, Helmut Haas, David W Dunne, Anne Cooke, Paola Zaccone
The T2 ribonuclease omega-1 is a powerful Th2-inducing factor secreted by the eggs of the blood fluke Schistosoma mansoni. Omega-1 can modulate pattern recognition receptor-induced inflammatory signatures and alter antigen presentation by dendritic cells. Recent findings have suggested that component(s) contained in or secreted by S. mansoni eggs (soluble egg antigen) can also enhance IL-1β secretion by dendritic cells stimulated with pattern recognition receptor ligands. Here we show that omega-1 enhances IL-1β secretion in macrophages stimulated with Toll-like receptor 2 ligand, and propose omega-1 as the factor in soluble egg antigen capable of regulating inflammasome activity...
November 2015: International Journal for Parasitology
https://www.readbyqxmd.com/read/26361229/indoleamine-2-3-dioxygenase-is-involved-in-the-inflammation-response-of-corneal-epithelial-cells-to-aspergillus-fumigatus-infections
#19
Nan Jiang, Guiqiu Zhao, Jing Lin, Liting Hu, Chengye Che, Cui Li, Qian Wang, Qiang Xu, Xudong Peng
Indoleamine 2,3-dioxygenase (IDO), which is mainly expressed in activated dendritic cells, is known as a regulator of immune responses. However, the role of IDO in immune responses against fungal corneal infection has not been investigated. To evaluate the regulatory mechanisms of IDO in fungal inflammation, we resorted to human corneal epithelial cells (HCECs), known as the first barrier of cornea against pathogenic microorganisms. We found that IDO was significantly up-regulated in corneal epithelium infected with Aspergillus fumigatus (A...
2015: PloS One
https://www.readbyqxmd.com/read/26352598/dectin-1-polymorphism-a-genetic-disease-specifier-in-autism-spectrum-disorders
#20
Meriem Bennabi, Richard Delorme, José Oliveira, Catherine Fortier, Mohamed Lajnef, Wahid Boukouaci, Jean-Paul Feugeas, François Marzais, Alexandru Gaman, Dominique Charron, Bijan Ghaleh, Rajagopal Krishnamoorthy, Marion Leboyer, Ryad Tamouza
INTRODUCTION: In autism spectrum disorders (ASD), complex gene-environment interactions contribute to disease onset and progress. Given that gastro-intestinal dysfunctions are common in ASD, we postulated involvement of microbial dysbiosis in ASD and investigated, under a case-control design, the influence of DNA polymorphisms in the CLEC7A gene that encodes a pivotal fungal sensor, Dectin-1. MATERIAL AND METHODS: DNAs from 478 ASD patients and 351 healthy controls (HC) were analyzed for the CLEC7A rs16910631G/A and rs2078178 A/G single nucleotide polymorphisms (SNPs)...
2015: PloS One
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