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Dectin-2

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https://www.readbyqxmd.com/read/28326063/lactobacillus-reuteri-surface-mucus-adhesins-upregulate-inflammatory-responses-through-interactions-with-innate-c-type-lectin-receptors
#1
Krisztián P Bene, Devon W Kavanaugh, Charlotte Leclaire, Allan P Gunning, Donald A MacKenzie, Alexandra Wittmann, Ian D Young, Norihito Kawasaki, Eva Rajnavolgyi, Nathalie Juge
The vertebrate gut symbiont Lactobacillus reuteri exhibits strain-specific adhesion and health-promoting properties. Here, we investigated the role of the mucus adhesins, CmbA and MUB, upon interaction of L. reuteri ATCC PTA 6475 and ATCC 53608 strains with human monocyte-derived dendritic cells (moDCs). We showed that mucus adhesins increased the capacity of L. reuteri strains to interact with moDCs and promoted phagocytosis. Our data also indicated that mucus adhesins mediate anti- and pro-inflammatory effects by the induction of interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α), IL-1β, IL-6, and IL-12 cytokines...
2017: Frontiers in Microbiology
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
#2
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...
March 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28282442/characterization-of-c-type-lectins-reveals-an-unexpectedly-limited-interaction-between-cryptococcus-neoformans-spores-and-dectin-1
#3
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/28193608/dectin-2-deficiency-modulates-th1-differentiation-and-improves-wound-healing-after-myocardial-infarction
#4
Xiaoxiang Yan, Hang Zhang, Qin Fan, Jian Hu, Rong Tao, Qiujing Chen, Yoichiro Iwakura, Weifeng Shen, Lin Lu, Qi Zhang, Ruiyan Zhang
Rationale: Macrophages are involved in wound healing after myocardial infarction (MI). The role of Dectin-2, a pattern recognition receptor mainly expressed on myeloid cells, in the infarct healing remains unknown. Objective: To determine whether Dectin-2 signaling is involved in the healing process and cardiac remodeling after MI, and to elucidate the underlying molecular mechanisms. Methods and Results: In a mouse model of permanent coronary ligation, Dectin-2, mainly expressed in macrophages, was shown to be increased in the early phase after MI...
February 13, 2017: Circulation Research
https://www.readbyqxmd.com/read/28046067/c-type-lectin-receptor-dectin-2-binds-to-an-endogenous-protein-%C3%AE-glucuronidase-on-dendritic-cells
#5
Daiki Mori, Kensuke Shibata, Sho Yamasaki
C-type lectin receptors (CLRs) recognize pathogen-derived ligands and abnormal self that trigger protective immune responses. However, the precise nature of self ligands recognized by CLRs remains to be determined. Here, we found that Dectin-2 recognizes bone marrow-derived dendritic cells (BMDCs) using Dectin-2-expressing reporter cells. This activity was inhibited by an excessive amount of mannose, and by the mutation of mannose-binding motif in Dectin-2. β-glucuronidase (Gusb) was identified as a protein bound to Dectin-2 and mutations of N-glycosylation sites in Gusb impaired the binding of Gusb to Dectin-2...
2017: PloS One
https://www.readbyqxmd.com/read/28027502/bioactive-polysaccharide-based-ph-sensitive-polymers-for-cytoplasmic-delivery-of-antigen-and-activation-of-antigen-specific-immunity
#6
Eiji Yuba, Ayaka Yamaguchi, Yuta Yoshizaki, Atsushi Harada, Kenji Kono
For establishment of cancer immunotherapy, antigen carriers are needed which have functions not only to deliver antigen into cytosol of dendritic cells (DCs), which induces antigen-specific cellular immune responses, but also to activate DCs. We previously reported cytoplasmic delivery of antigen using liposomes modified with pH-sensitive polymers such as carboxylated poly(glycidol)s or dextran. Modification using these polymers provides stable liposomes with pH-sensitive fusogenic/membrane-disruptive ability...
December 22, 2016: Biomaterials
https://www.readbyqxmd.com/read/27926862/vav-proteins-are-key-regulators-of-card9-signaling-for-innate-antifungal-immunity
#7
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/27872290/the-innate-immune-receptor-dectin-2-mediates-the-phagocytosis-of-cancer-cells-by-kupffer-cells-for-the-suppression-of-liver-metastasis
#8
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...
December 6, 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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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