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https://www.readbyqxmd.com/read/29352133/molecular-and-physiological-roles-of-the-adaptor-protein-card9-in-immunity
#1
REVIEW
Xiaoming Zhong, Bin Chen, Liang Yang, Zhiwen Yang
CARD9 is a caspase recruitment domain-containing signaling protein that plays a critical role in innate and adaptive immunity. It has been widely demonstrated that CARD9 adaptor allows pattern recognition receptors to induce NF-κB and MAPK activation, which initiates a "downstream" inflammation cytokine cascade and provides effective protection against microbial invasion, especially fungal infection. Here our aim is to update existing paradigms and summarize the most recent findings on the CARD9 signaling pathway, revealing significant mechanistic insights into the pathogenesis of CARD9 deficiency...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29249317/chicken-macrophages-infected-with-salmonella-s-enteritidis-or-s-heidelberg-produce-differential-responses-in-immune-and-metabolic-signaling-pathways
#2
Haiqi He, Ryan J Arsenault, Kenneth J Genovese, Casey Johnson, Michael H Kogut
Protein kinases act in coordination with phosphatases to control protein phosphorylation and regulate signaling pathways and cellular processes involved in nearly every functions of cell life. Salmonella are known to manipulate the host kinase network to gain entrance and survive inside host cells. The effect of Salmonella infection on the host kinase network has been studied in mammalian cells, but information is largely lacking in chicken immune cells. Our previous study indicated that chicken macrophage cells respond differentially to different Salmonella strains...
January 2018: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29199562/immunomodulatory-effects-of-extracellular-%C3%AE-glucan-isolated-from-the-king-oyster-mushroom-pleurotus-eryngii-agaricomycetes-and-its-sulfated-form-on-signaling-molecules-involved-in-innate-immunity
#3
Yong Hyun Kim, Eui-Gil Jung, Kook-Il Han, Bharat Bhusan Patnaik, Hyun-Jung Kwon, Hyoun-Su Lee, Wan Jong Kim, Man-Deuk Han
The aim of this study was to determine, using murine RAW 264.7 macrophages, the immunomodulatory effect of extracellular β-glucan isolated from Pleurotus eryngii (PEBG) and its sulfated derivative (PEBG-S) on signaling molecules implicated in host innate immunity. β-Glucan was extracted and purified from the mycelial culture using optimal medium concentrations. It was then chemically converted to its sulfated form. Monosaccharide composition of β-glucan was characterized with p-aminobenzoic acid ethyl ester-derivatized sugars through highperformance liquid chromatography analysis...
2017: International Journal of Medicinal Mushrooms
https://www.readbyqxmd.com/read/29169147/c-type-lectin-receptors-in-anti-fungal-immunity
#4
REVIEW
Moe Shiokawa, Sho Yamasaki, Shinobu Saijo
Host immune systems are constantly engaged with fungal pathogens which are common in environments as well as in healthy human skin and mucosa. C-type lectin receptors (CLRs) are expressed in myeloid cells and play central roles in host defenses against fungal infections by coordinating innate and adaptive immune systems. Upon ligand binding, CLRs stimulate cellular responses by inducing the production of cytokines and reactive oxygen species via the Syk/CARD9 signaling pathway, leading to fungal elimination...
November 20, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29128761/inborn-errors-of-immunity-underlying-fungal-diseases-in-otherwise-healthy-individuals
#5
REVIEW
Juan Li, Donald C Vinh, Jean-Laurent Casanova, Anne Puel
It has been estimated that there are at least 1.5 million fungal species, mostly present in the environment, but only a few of these fungi cause human disease. Most fungal diseases are self-healing and benign, but some are chronic or life-threatening. Acquired and inherited defects of immunity, including breaches of mucocutaneous barriers and circulating leukocyte deficiencies, account for most severe modern-day mycoses. Other types of infection typically accompany these fungal infections. More rarely, severe fungal diseases can strike otherwise healthy individuals...
November 9, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29100328/the-interaction-effect-of-rs4077515-and-rs17019602-increases-the-susceptibility-to-iga-nephropathy
#6
Changwei Wu, Guisen Li, Li Wang
Background: Immunoglobulin A nephropathy (IgAN), the most common form of primary glomerular diseases worldwide, is a complex multifactorial disease. Previous genome wide association studies (GWAS) reported that variants CARD9 and VAV3 genes were associated with immunoregulation and susceptibility to IgAN. In this study, we further validated the associations and explored the interaction effect of rs4077515 and rs17019602 in IgAN patients. Results: There was no significant correlation between the two variants and IgAN (P > 0...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29080677/impaired-specific-anti-fungal-immunity-in-card9-deficient-patients-with-phaeohyphomycosis
#7
Xiaowen Wang, Ruijun Zhang, Weiwei Wu, Yinggai Song, Zhe Wan, Wenling Han, Ruoyu Li
Phaeohyphomycosis is a group of severe infections caused by dematiaceous fungi. We previously identified CARD9 deficiencies in four Chinese patients with phaeohyphomycosis caused by Phialophora verrucosa. In this study, we sought to identify the genetic and immunological mechanisms underlying rare dematiaceous fungal infections in three otherwise healthy patients with phaeohyphomycosis caused by Exophiala spinifera, Ochroconis musae, and Corynespora cassiicola. CARD9 sequencing in these patients revealed one novel mutation (p...
October 25, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29073062/small-molecule-inhibitors-directly-target-card9-and-mimic-its-protective-variant-in-inflammatory-bowel-disease
#8
Elizaveta S Leshchiner, Jason S Rush, Michael A Durney, Zhifang Cao, Vlado Dančík, Benjamin Chittick, Huixian Wu, Adam Petrone, Joshua A Bittker, Andrew Phillips, Jose R Perez, Alykhan F Shamji, Virendar K Kaushik, Mark J Daly, Daniel B Graham, Stuart L Schreiber, Ramnik J Xavier
Advances in human genetics have dramatically expanded our understanding of complex heritable diseases. Genome-wide association studies have identified an allelic series of CARD9 variants associated with increased risk of or protection from inflammatory bowel disease (IBD). The predisposing variant of CARD9 is associated with increased NF-κB-mediated cytokine production. Conversely, the protective variant lacks a functional C-terminal domain and is unable to recruit the E3 ubiquitin ligase TRIM62. Here, we used biochemical insights into CARD9 variant proteins to create a blueprint for IBD therapeutics and recapitulated the mechanism of the CARD9 protective variant using small molecules...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28984994/novel-bi-allelic-splice-mutations-in-card9-causing-adult-onset-candida-endophthalmitis
#9
Christina Gavino, Sibylle Mellinghoff, Oliver A Cornely, Marija Landekic, Catherine Le, Melanie Langelier, Makan Golizeh, Susanna Proske, Donald C Vinh
BACKGROUND: CARD9 deficiency (CANDF2; OMIM# 212050) is an autosomal-recessive monogenic inborn error of immunity conferring susceptibility to invasive fungal diseases, including the very distinct syndrome of spontaneous central nervous system candidiasis, in which opportunistic yeasts of the genus Candida infect the central nervous system (either brain parenchyma and/or meninges) in the absence of trauma, chemotherapy or underlying systemic disease. METHODS: We present a patient with spontaneous endophthalmitis of the right eye due to Candida albicans; further investigations revealed concomitant cerebral abscess...
October 6, 2017: Mycoses
https://www.readbyqxmd.com/read/28842327/genome-wide-analysis-of-protein-coding-variants-in-leprosy
#10
Hong Liu, Zhenzhen Wang, Yi Li, Gongqi Yu, Xi'an Fu, Chuan Wang, Wenting Liu, Yongxiang Yu, Fangfang Bao, Astrid Irwanto, Jian Liu, Tongsheng Chu, Anand Kumar Andiappan, Sebastian Maurer-Stroh, Vachiranee Limviphuvadh, Honglei Wang, Zihao Mi, Yonghu Sun, Lele Sun, Ling Wang, Chaolong Wang, Jiabao You, Jinghui Li, Jia Nee Foo, Herty Liany, Wee Yang Meah, Guiye Niu, Zhenhua Yue, Qing Zhao, Na Wang, Meiwen Yu, Wenjun Yu, Xiujun Cheng, Chiea Chuen Khor, Kar Seng Sim, Tin Aung, Ningli Wang, Deyun Wang, Li Shi, Yong Ning, Zhongyi Zheng, Rongde Yang, Jinlan Li, Jun Yang, Liangbin Yan, Jianping Shen, Guocheng Zhang, Shumin Chen, Jianjun Liu, Furen Zhang
Although genome-wide association studies have greatly advanced our understanding of the contribution of common noncoding variants to leprosy susceptibility, protein-coding variants have not been systematically investigated. We carried out a three-stage genome-wide association study of protein-coding variants in Han Chinese, of whom were 7,048 leprosy patients and 14,398 were healthy control subjects. Seven coding variants of exome-wide significance were discovered, including two rare variants: rs145562243 in NCKIPSD (P = 1...
August 24, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28793349/ligation-of-dectin-2-with-a-novel-microbial-ligand-promotes-adjuvant-activity-for-vaccination
#11
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 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28790160/card9-mediates-susceptibility-to-intestinal-pathogens-through-microbiota-modulation-and-control-of-bacterial-virulence
#12
Bruno Lamas, Marie-Laure Michel, Nadine Waldschmitt, Hang-Phuong Pham, Vassiliki Zacharioudaki, Louise Dupraz, Myriam Delacre, Jane M Natividad, Gregory Da Costa, Julien Planchais, Bruno Sovran, Chantal Bridonneau, Adrien Six, Philippe Langella, Mathias L Richard, Mathias Chamaillard, Harry Sokol
OBJECTIVE: In association with innate and adaptive immunity, the microbiota controls the colonisation resistance against intestinal pathogens. Caspase recruitment domain 9 (CARD9), a key innate immunity gene, is required to shape a normal gut microbiota. Card9(-/-) mice are more susceptible to the enteric mouse pathogen Citrobacter rodentium that mimics human infections with enteropathogenic and enterohaemorrhagic Escherichia coli. Here, we examined how CARD9 controls C. rodentium infection susceptibility through microbiota-dependent and microbiota-independent mechanisms...
August 8, 2017: Gut
https://www.readbyqxmd.com/read/28765954/in%C3%A2-vitro-reconstitution-of-interactions-in-the-card9-signalosome
#13
Jin Hee Park, Jae Young Choi, Mir Faisal Mustafa, Hyun Ho Park
The caspase-associated recruitment domain (CARD)‑containing protein 9 (CARD9) signalosome is composed of CARD9, B‑cell CLL/lymphoma 10 (BCL10) and mucosa‑associated lymphoid tissue lymphoma translocation protein 1 (MALT1). The CARD9 signalosome has been reported to exert critical functions in the immunoreceptor tyrosine‑based activation motif‑coupled receptor‑mediated activation of myeloid cells, through nuclear factor‑κB pathways during innate immunity processes. During CARD9 signalosome assembly, BCL10 has been revealed to function as an adaptor protein and to interact with CARD9 via CARD‑CARD interactions; BCL10 also interacts with MALT1 via its C‑terminal Ser/Thr‑rich region and the first immunoglobulin domain of MALT1...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28763100/fungal-derived-cues-promote-ocular-autoimmunity-through-a-dectin-2-card9-mediated-mechanism
#14
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/28640392/calcineurin-inhibitors-exacerbate-coronary-arteritis-via-the-myd88-signalling-pathway-in-a-murine-model-of-kawasaki-disease
#15
K Murata, Y Motomura, T Tanaka, S Kanno, T Yano, M Onimaru, A Shimoyama, H Nishio, Y Sakai, M Oh-Hora, H Hara, K Fukase, H Takada, S Masuda, S Ohga, S Yamasaki, T Hara
Calcineurin inhibitors (CNIs) have been used off-label for the treatment of refractory Kawasaki disease (KD). However, it remains unknown whether CNIs show protective effects against the development of coronary artery lesions in KD patients. To investigate the effects of CNIs on coronary arteries and the mechanisms of their actions on coronary arteritis in a mouse model of KD, we performed experiments with FK565, a ligand of nucleotide-binding oligomerization domain-containing protein 1 (NOD1) in wild-type, severe combined immunodeficiency (SCID), caspase-associated recruitment domain 9 (CARD9)(-/-) and myeloid differentiation primary response gene 88 (MyD88)(-/-) mice...
October 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28620967/contribution-of-card9-mediated-signalling-to-wound-healing-in-skin
#16
Emi Kanno, Kazuyoshi Kawakami, Hiromasa Tanno, Aiko Suzuki, Noriko Sato, Airi Masaki, Ayano Imamura, Naoyuki Takagi, Takayuki Miura, Hideki Yamamoto, Keiko Ishii, Hiromitsu Hara, Yoshimichi Imai, Ryoko Maruyama, Masahiro Tachi
The inflammatory response after skin injury involves the secretion of a variety of cytokines and growth factors that are necessary for tissue repair. Caspase recruitment domain-containing protein 9 (CARD9) is an essential signalling adaptor molecule for NF-κB activation upon triggering through C-type lectin receptors (CLRs), which are expressed in macrophages and dendritic cells. However, the role of CARD9 in inflammatory responses at the wound site has not been elucidated. In this study, we analysed the role of CARD9 in the healing process of skin wounds...
November 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28586167/card9-dependent-il-1%C3%AE-regulates-il-22-production-from-group-3-innate-lymphoid-cells-and-promotes-colitis-associated-cancer
#17
Hanna Bergmann, Susanne Roth, Konstanze Pechloff, Elina A Kiss, Sabine Kuhn, Mathias Heikenwälder, Andreas Diefenbach, Florian R Greten, Jürgen Ruland
Inflammatory bowel diseases (IBD) are key risk factors for the development of colorectal cancer, but the mechanisms that link intestinal inflammation with carcinogenesis are insufficiently understood. Card9 is a myeloid cell-specific signaling protein that regulates inflammatory responses downstream of various pattern recognition receptors and which cooperates with the inflammasomes for IL-1β production. Because polymorphisms in Card9 were recurrently associated with human IBD, we investigated the function of Card9 in a colitis-associated cancer (CAC) model...
August 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28494724/c-type-lectin-receptor-old-friend-and-new-player
#18
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/28399013/caspase-recruitment-domain-9-microbiota-and-tryptophan-metabolism-dangerous-liaisons-in-inflammatory-bowel-diseases
#19
Bruno Lamas, Mathias L Richard, Harry Sokol
PURPOSE OF REVIEW: Inflammatory bowel diseases (IBDs) develop as a result of a combination of genetic predisposition, dysbiosis of the gut microbiota, and environmental influences. Here, we describe an example of how caspase recruitment domain 9 (CARD9), one of the numerous IBD susceptibility genes, participate to colitis susceptibility by shaping gut microbiota to produce tryptophan metabolites. RECENT FINDINGS: Recent study showed that CARD9 mice are more susceptible to colitis as a result of impaired interleukin 22 signaling pathway...
July 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28391957/dermatophytic-disease-with-deficit-in-card9-a-new-case-with-a-brain-impairment
#20
O Boudghene Stambouli, N Amrani, K Boudghéne Stambouli, F Bouali
INTRODUCTION: Dermatophytic disease individualized by Hadida and Schousboe in 1959 is a rare form of chronic dermatophyte infection; characterized by subcutaneous and visceral invasion and a therapeutic failure. We report a case of dermatophytic disease with brain abscess in an Algerian patient. OBSERVATIONS: The patient was 47-year-old, she was born parents first cousins. She had since the age of 10 years scaly scalp lesions that became secondarily papular and nodular...
April 5, 2017: Journal de Mycologie Médicale
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