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CARD9

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https://www.readbyqxmd.com/read/29777223/card9-s12n-facilitates-the-production-of-il-5-by-alveolar-macrophages-for-the-induction-of-type-2-immune-responses
#1
Xia Xu, Jin-Fu Xu, Guoxing Zheng, Hai-Wen Lu, Jie-Lin Duan, Wei Rui, Jian-Hong Guan, Li-Qing Cheng, Dan-Dan Yang, Ming-Chao Wang, Quan-Zhen Lv, Jian-Xiong Li, Xueqiang Zhao, Chun-Xia Chen, Peng Shi, Xin-Ming Jia, Xin Lin
The adaptor CARD9 functions downstream of C-type lectin receptors (CLRs) for the sensing of microbial infection, which leads to responses by the TH 1 and TH 17 subsets of helper T cells. The single-nucleotide polymorphism rs4077515 at CARD9 in the human genome, which results in the substitution S12N (CARD9S12N ), is associated with several autoimmune diseases. However, the function of CARD9S12N has remained unknown. Here we generated CARD9S12N knock-in mice and found that CARD9S12N facilitated the induction of type 2 immune responses after engagement of CLRs...
May 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29775695/pulsatilla-decoction-inhibits-candida-albicans-proliferation-and-adhesion-in-a-mouse-model-of-vulvovaginal-candidiasis-via-the-dectin-1-signaling-pathway
#2
Lilin Yang, Haiwang Wu, Weiyu Qiu, Longyi Guo, Xin Du, Qingying Yu, Jie Gao, Songping Luo
ETHNOPHARMACOLOGICAL RELEVANCE: Pulsatilla decoction (PD) is a classical prescription in Traditional Chinese Medicine (TCM) and has been reported to have inhibitory effects on Candida albicans proliferation. STUDY AIM: To investigate the therapeutic effects of PD in the treatment of Vulvovaginal candidiasis (VVC) and elucidate the potential mechanism. MATERIALS AND METHODS: Female BALB/c mice (N=90) were randomized to six treatment groups, including the Control group, Model group, three PD groups and Fluconazole group which served as a positive control (20mg/kg weekly)...
May 15, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29713904/gene-expression-changes-in-the-retina-after-systemic-administration-of-aldosterone
#3
Aoi Ono, Kazuyuki Hirooka, Yuki Nakano, Eri Nitta, Akira Nishiyama, Akitaka Tsujikawa
PURPOSE: Retinal ganglion cell (RGC) loss associated with thinning of the retinal nerve fiber layer without elevated intraocular pressure (IOP) occurs after the systemic administration of aldosterone. Since it is important to determine the mechanism of cell death independent of the IOP, we examined gene expression changes in the retina after the systemic administration of aldosterone. METHODS: Following subcutaneous implantation of an osmotic minipump into the mid-scapular region of rats, we administered an 80 μg/kg/day dose of aldosterone...
April 30, 2018: Japanese Journal of Ophthalmology
https://www.readbyqxmd.com/read/29675414/spondyloarthritis-acute-anterior-uveitis-and-fungi-updating-the-catterall-king-hypothesis
#4
Martin Laurence, Mark Asquith, James T Rosenbaum
Spondyloarthritis is a common type of arthritis which affects mostly adults. It consists of idiopathic chronic inflammation of the spine, joints, eyes, skin, gut, and prostate. Inflammation is often asymptomatic, especially in the gut and prostate. The HLA-B*27 allele group, which presents intracellular peptides to CD8+ T cells, is by far the strongest risk factor for spondyloarthritis. The precise mechanisms and antigens remain unknown. In 1959, Catterall and King advanced a novel hypothesis explaining the etiology of spondyloarthritis: an as-yet-unrecognized sexually acquired microbe would be causing all spondyloarthritis types, including acute anterior uveitis...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29659908/prototheca-zopfii-colitis-in-inherited-card9-deficiency
#5
Sinan Sari, Buket Dalgic, Atis Muehlenbachs, Marlene DeLeon-Carnes, Cynthia S Goldsmith, Ozgur Ekinci, Dhanpat Jain, M Kelly Keating, Silvia Vilarinho
Human protothecosis is a rare microalgae infection, and its dissemination typically occurs in immunocompromised individuals, but no specific immune defect has been reported. Here, we describe an 8-year-old daughter of a consanguineous union with abdominal pain and bloody diarrhea for 3 months who was found to have pancolitis with numerous microalgae identified as Prototheca zopfii. In the absence of a known immunodeficiency, exome sequencing was performed and uncovered a novel recessive frameshift mutation in CARD9 (p...
April 6, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29575791/the-essential-function-of-card9-in-diet-induced-inflammation-and-metabolic-disorders-in-mice
#6
Xuejiao Zeng, Xihao Du, Jia Zhang, Shuo Jiang, Jie Liu, Yuquan Xie, Wei Shan, Guanglong He, Qinghua Sun, Jinzhuo Zhao
Inflammation and metabolic disorder are common pathophysiological conditions, which play a vital role in the development of obesity and type 2 diabetes. The purpose of this study was to explore the effects of caspase recruitment domain (CARD) 9 in the high fat diet (HFD)-treated mice and attempt to find a molecular therapeutic target for obesity development and treatment. Sixteen male CARD9-/- and corresponding male WT mice were fed with normal diet or high fat diet, respectively, for 12 weeks. Glucose tolerance, insulin resistance, oxygen consumption and heat production of the mice were detected...
March 25, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29487599/dectin-1-syk-card9-signaling-pathway-in-tb-immunity
#7
REVIEW
Matthew Wagener, J Claire Hoving, Hlumani Ndlovu, Mohlopheni J Marakalala
One of the first steps toward mounting an effective immune response to Mycobacterium tuberculosis (Mtb) is recognition of the pathogen through pattern-recognition receptors (PRRs) expressed by innate immune cells. Activation of the PRR Dectin-1 by an unknown mycobacterial ligand triggers an intracellular signaling cascade involving numerous proteins, including spleen tyrosine kinase, protein kinase C-delta, and caspase recruitment domain family member 9, some of which have been shown to influence host immune response to TB infection...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29482417/microbial-co-infection-alters-macrophage-polarization-phagosomal-escape-and-microbial-killing
#8
Nikita H Trivedi, Jieh-Juen Yu, Chiung-Yu Hung, Richard P Doelger, Christopher S Navara, Lisa Y Armitige, Janakiram Seshu, Anthony P Sinai, James P Chambers, M Neal Guentzel, Bernard P Arulanandam
Macrophages are important innate immune cells that respond to microbial insults. In response to multi-bacterial infection, the macrophage activation state may change upon exposure to nascent mediators, which results in different bacterial killing mechanism(s). In this study, we utilized two respiratory bacterial pathogens, Mycobacterium bovis (Bacillus Calmette Guẻrin, BCG) and Francisella tularensis live vaccine strain (LVS) with different phagocyte evasion mechanisms, as model microbes to assess the influence of initial bacterial infection on the macrophage response to secondary infection...
April 2018: Innate Immunity
https://www.readbyqxmd.com/read/29402133/featured-article-immunomodulatory-effect-of-hemozoin-on-pneumocyte-apoptosis-via-card9-pathway-a-possibly-retarding-pulmonary-resolution
#9
Sitang Maknitikul, Natthanej Luplertlop, Urai Chaisri, Yaowapa Maneerat, Sumate Ampawong
Plasmodium falciparum, the most virulent malaria parasite species, causes severe symptoms especially acute lung injury (ALI), of which characterized by alveolar epithelium and endothelium destruction and accelerated to blood-gas-barrier breakdown. Parasitized erythrocytes, endothelial cells, monocytes, and cytokines are all involved in this mechanism, but hemozoin (HZ), the parasitic waste from heme detoxification, also mainly contributes. In addition, it is not clear why type II pneumocyte proliferation, alveolar restorative stage, is rare in malaria-associated ALI...
March 2018: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29386115/cd209a-synergizes-with-dectin-2-and-mincle-to-drive-severe-th17-cell-mediated-schistosome-egg-induced-immunopathology
#10
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/29352133/molecular-and-physiological-roles-of-the-adaptor-protein-card9-in-immunity
#11
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
#12
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
#13
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
#14
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...
December 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29128761/inborn-errors-of-immunity-underlying-fungal-diseases-in-otherwise-healthy-individuals
#15
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...
December 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29100328/the-interaction-effect-of-rs4077515-and-rs17019602-increases-the-susceptibility-to-iga-nephropathy
#16
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-antifungal-immunity-in-card9-deficient-patients-with-phaeohyphomycosis
#17
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 showed one mutation (p...
March 2018: 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
#18
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
#19
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
#20
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...
December 2017: Journal of Investigative Dermatology
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