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Dectin-2

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https://www.readbyqxmd.com/read/28793349/ligation-of-dectin-2-with-a-novel-microbial-ligand-promotes-adjuvant-activity-for-vaccination
#1
Huafeng Wang, Taek-Jin Lee, Scott J Fites, Richard Merkhofer, Robert Zarnowski, Tristan Brandhorst, Kevin Galles, Bruce Klein, Marcel Wüthrich
The development of vaccines against fungi and other intracellular microbes is impeded in part by a lack of suitable adjuvants. While most current vaccines against infectious diseases preferentially induce production of antibodies, cellular immunity is essential for the resolution of fungal infections. Microbes such as fungi and Mycobacterium tuberculosis require Th17 and Th1 cells for resistance, and engage the C-type lectin receptors including Dectin-2. Herein, we discovered a novel Dectin-2 ligand, the glycoprotein Blastomyces Eng2 (Bl-Eng2)...
August 9, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28763100/fungal-derived-cues-promote-ocular-autoimmunity-through-a-dectin-2-card9-mediated-mechanism
#2
Brieanna R Brown, Ellen J Lee, Paige E Snow, Emily E Vance, Yoichiro Iwakura, Naohito Ohno, Noriko Miura, Xin Lin, Gordon D Brown, Christine A Wells, Justine R Smith, Rachel R Caspi, Holly L Rosenzweig
Uveitis (intraocular inflammation) is a leading cause of vision loss. Although its etiology 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, interphotoceptor retinoid binding protein (IRBP), in combination with mycobacteria-containing CFA, has many clinical and histopathological features of human posterior uveitis...
August 1, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28671985/dectin-2-is-a-primary-receptor-for-nlrp3-inflammasome-activation-in-dendritic-cell-response-to-histoplasma-capsulatum
#3
Tzu-Hsuan Chang, Juin-Hua Huang, Hsiu-Chao Lin, Wen-Yu Chen, Yu-Hsiang Lee, Li-Chung Hsu, Mihai G Netea, Jenny P-Y Ting, Betty A Wu-Hsieh
Inflammasome is an intracellular protein complex that serves as cytosolic pattern recognition receptor (PRR) to engage with pathogens and to process cytokines of the interleukin-1 (IL-1) family into bioactive molecules. It has been established that interleukin-1β (IL-1β) is important to host defense against Histoplasma capsulatum infection. However, the detailed mechanism of how H. capsulatum induces inflammasome activation leading to IL-1β production has not been studied. Here, we showed in dendritic cells (DCs) that H...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28658592/dectin-1-plays-an-important-role-in-host-defense-against-systemic-candida-glabrata-infection
#4
Si Min Chen, Hui Shen, Teng Zhang, Xin Huang, Xiao Qi Liu, Shi Yu Guo, Jing Jun Zhao, Chun Fang Wang, Lan Yan, Guo Tong Xu, Yuan Ying Jiang, Mao Mao An
Candida glabrata is the second most common pathogen of severe candidiasis in immunocompromised hosts, following C. albicans. Although C. glabrata and C. albicans belong to the same genus, they are phylogenetically distinct. C-type lectin receptors (CLRs), acting as pattern-recognition receptors (PRRs), play critical roles in host defense against C. albicans infections. However, our understanding of the specific roles of CLRs in host defense against C. glabrata is limited. Here, we explored the potential roles of the C-type lectins Dectin-1 and Dectin-2 in host defense against C...
June 28, 2017: Virulence
https://www.readbyqxmd.com/read/28652405/mechanism-of-pathogen-recognition-by-human-dectin-2
#5
Hadar Feinberg, Sabine A F Jégouzo, Maximus J Rex, Kurt Drickamer, William I Weis, Maureen E Taylor
Dectin-2, a C-type lectin on macrophages and other cells of the innate immune system, functions in response to pathogens, particularly fungi. The carbohydrate-recognition domain (CRD) in dectin-2 is linked to a transmembrane sequence that interacts with the common Fc receptor γ subunit to initiate immune signaling. The molecular mechanism by which dectin-2 selectively binds to pathogens has been investigated by characterizing the CRD expressed in a bacterial system. Competition binding studies indicated that the CRD binds to monosaccharides with modest affinity and that affinity was greatly enhanced for mannose-linked α1-2 or α1-4 to a second mannose residue...
August 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28566659/effects-of-natural-and-chemically-defined-nutrients-on-candida-albicans-water-soluble-fraction-caws-vasculitis-in-mice
#6
Wataru Sato, Ken-Ichi Ishibashi, Daisuke Yamanaka, Yoshiyuki Adachi, Naohito Ohno
Kawasaki disease (KD) is an inflammatory disease that was identified by Professor Tomisaku Kawasaki in 1961. Candida albicans-derived substances, such as C. albicans water-soluble fraction (CAWS) , induce coronary arteritis similar to KD in mice. CAWS functions as a pathogen-associated molecular pattern (PAMP) by acting as a ligand for dectin-2. A gut-associated immunological system has developed specifically to segregate advantageous and detrimental stimuli, and the microbial flora has been found to markedly affect the development and severity of diseases...
2017: Medical Mycology Journal
https://www.readbyqxmd.com/read/28494724/c-type-lectin-receptor-old-friend-and-new-player
#7
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/28440726/expression-of-c-type-lectin-receptor-mrna-in-chronic-otitis-media-with-cholesteatoma
#8
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/28326063/lactobacillus-reuteri-surface-mucus-adhesins-upregulate-inflammatory-responses-through-interactions-with-innate-c-type-lectin-receptors
#9
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
#10
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/28282442/characterization-of-c-type-lectins-reveals-an-unexpectedly-limited-interaction-between-cryptococcus-neoformans-spores-and-dectin-1
#11
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
#12
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: The aim of this study is 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...
March 31, 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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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