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https://www.readbyqxmd.com/read/28158919/zinc-rescues-obesity-induced-cardiac-hypertrophy-via-stimulating-metallothionein-to-suppress-oxidative-stress-activated-bcl10-card9-p38-mapk-pathway
#1
Shudong Wang, Junlian Gu, Zheng Xu, Zhiguo Zhang, Tao Bai, Jianxiang Xu, Jun Cai, Gregory Barnes, Qiu-Ju Liu, Jonathan H Freedman, Yonggang Wang, Quan Liu, Yang Zheng, Lu Cai
Obesity often leads to obesity-related cardiac hypertrophy (ORCH), which is suppressed by zinc-induced inactivation of p38 mitogen-activated protein kinase (p38 MAPK). In this study, we investigated the mechanisms by which zinc inactivates p38 MAPK to prevent ORCH. Mice (4-week old) were fed either high fat diet (HFD, 60% kcal fat) or normal diet (ND, 10% kcal fat) containing variable amounts of zinc (deficiency, normal and supplement) for 3 and 6 months. P38 MAPK siRNA and the p38 MAPK inhibitor SB203580 were used to suppress p38 MAPK activity in vitro and in vivo, respectively...
February 3, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28143983/rim-pathway-mediated-alterations-in-the-fungal-cell-wall-influence-immune-recognition-and-inflammation
#2
Kyla S Ost, Shannon K Esher, Chrissy M Leopold Wager, Louise Walker, Jeanette Wagener, Carol Munro, Floyd L Wormley, J Andrew Alspaugh
: Compared to other fungal pathogens, Cryptococcus neoformans is particularly adept at avoiding detection by innate immune cells. To explore fungal cellular features involved in immune avoidance, we characterized cell surface changes of the C. neoformans rim101Δ mutant, a strain that fails to organize and shield immunogenic epitopes from host detection. These cell surface changes are associated with an exaggerated, detrimental inflammatory response in mouse models of infection. We determined that the disorganized strain rim101Δ cell wall increases macrophage detection in a contact-dependent manner...
January 31, 2017: MBio
https://www.readbyqxmd.com/read/28130494/oxidized-low-density-lipoprotein-immune-complex-priming-of-the-nlrp3-inflammasome-involves-tlr-and-fc%C3%AE-r-cooperation-and-is-dependent-on-card9
#3
Jillian P Rhoads, John R Lukens, Ashley J Wilhelm, Jared L Moore, Yanice Mendez-Fernandez, Thirumala-Devi Kanneganti, Amy S Major
Oxidized low-density lipoprotein (oxLDL) is known to activate inflammatory responses in a variety of cells, especially macrophages and dendritic cells. Interestingly, much of the oxLDL in circulation is complexed to Abs, and these resulting immune complexes (ICs) are a prominent feature of chronic inflammatory disease, such as atherosclerosis, type-2 diabetes, systemic lupus erythematosus, and rheumatoid arthritis. Levels of oxLDL ICs often correlate with disease severity, and studies demonstrated that oxLDL ICs elicit potent inflammatory responses in macrophages...
January 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28090315/chronic-mucocutaneous-candidiasis-disease-associated-with-inborn-errors-of-il-17-immunity
#4
REVIEW
Satoshi Okada, Anne Puel, Jean-Laurent Casanova, Masao Kobayashi
Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections affecting the nails, skin and oral and genital mucosae caused by Candida spp., mainly Candida albicans. CMC is an infectious phenotype in patients with inherited or acquired T-cell deficiency. Patients with autosomal-dominant (AD) hyper IgE syndrome (HIES), AD signal transducer and activator of transcription 1 (STAT1) gain-of-function, autosomal-recessive (AR) deficiencies in interleukin (IL)-12 receptor β1 (IL-12Rβ1), IL-12p40, caspase recruitment domain-containing protein 9 (CARD9) or retinoic acid-related orphan receptor γT (RORγT) or AR autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) develop CMC as a major infectious phenotype that is categorized as Syndromic CMC...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28008832/-card9-is-involved-in-the-recovery-of-colitis-by-promoting-the-production-of-ahr-ligands-by-the-intestinal-microbiota
#5
Bruno Lamas, Mathias L Richard, Harry Sokol
No abstract text is available yet for this article.
November 2016: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/27957800/card9-gene-silencing-with-sirna-protects-rats-against-severe-acute-pancreatitis-card9-dependent-nf-%C3%AE%C2%BAb-and-p38mapks-pathway
#6
Zhi-Wen Yang, Xiao-Xiao Meng, Chun Zhang, Ping Xu
We previously reported the up-regulation of caspase recruitment domain 9 (CARD9) expressions in severe acute pancreatitis (SAP) patients, but little is known about its regulation. In this study, small interfering RNA (siRNA) was used to reduce the levels of CARD9 expression in sodium taurocholate-stimulated SAP rats. CARD9 was overexpressed in SAP rats, which correlated with the severity of pancreatitis. When compared to the untreated group, the cohort that received the siRNA treatment demonstrated a significant reduction in pancreatic injury, neutrophil infiltration, myeloperoxidase activity and pro-inflammatory cytokines...
December 13, 2016: Journal of Cellular and Molecular Medicine
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/27920495/card9-as-a-potential-target-in-cardiovascular-disease
#8
REVIEW
Matthew R Peterson, Samantha E Haller, Jun Ren, Sreejayan Nair, Guanglong He
Systemic inflammation and localized macrophage infiltration have been implicated in cardiovascular pathologies, including coronary artery disease, carotid atherosclerosis, heart failure, obesity-associated heart dysfunction, and cardiac fibrosis. Inflammation induces macrophage infiltration and activation and release of cytokines and chemokines, causing tissue dysfunction by instigating a positive feedback loop that further propagates inflammation. Cytosolic adaptor caspase recruitment domain family, member 9 (CARD9) is a protein expressed primarily by dendritic cells, neutrophils, and macrophages, in which it mediates cytokine secretion...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27802154/interplay-of-host-genetics-and-gut-microbiota-underlying-the-onset-and-clinical-presentation-of-inflammatory-bowel-disease
#9
Floris Imhann, Arnau Vich Vila, Marc Jan Bonder, Jingyuan Fu, Dirk Gevers, Marijn C Visschedijk, Lieke M Spekhorst, Rudi Alberts, Lude Franke, Hendrik M van Dullemen, Rinze W F Ter Steege, Curtis Huttenhower, Gerard Dijkstra, Ramnik J Xavier, Eleonora A M Festen, Cisca Wijmenga, Alexandra Zhernakova, Rinse K Weersma
OBJECTIVE: Patients with IBD display substantial heterogeneity in clinical characteristics. We hypothesise that individual differences in the complex interaction of the host genome and the gut microbiota can explain the onset and the heterogeneous presentation of IBD. Therefore, we performed a case-control analysis of the gut microbiota, the host genome and the clinical phenotypes of IBD. DESIGN: Stool samples, peripheral blood and extensive phenotype data were collected from 313 patients with IBD and 582 truly healthy controls, selected from a population cohort...
October 8, 2016: Gut
https://www.readbyqxmd.com/read/27785786/the-genetic-background-of-inflammatory-bowel-disease-from-correlation-to-causality
#10
REVIEW
Werna Tc Uniken Venema, Michiel D Voskuil, Gerard Dijkstra, Rinse K Weersma, Eleonora Am Festen
Recent studies have greatly improved our insight into the genetic background of inflammatory bowel disease (IBD). New high-throughput technologies and large-scale international collaborations have contributed to the identification of 200 independent genetic risk loci for IBD. However, in most of these loci, it is unclear which gene conveys the risk for IBD. More importantly, it is unclear which variant within or near the gene is causal to the disease. Using targeted GWAS, imputation, resequencing of risk loci, and in silico fine-mapping of densely typed loci, several causal variants have been identified in IBD risk genes, and various pathological pathways have been uncovered...
January 2017: Journal of Pathology
https://www.readbyqxmd.com/read/27783709/correction-the-card9-polymorphisms-rs4077515-rs10870077-and-rs10781499-are-uncoupled-from-susceptibility-to-and-severity-of-pulmonary-tuberculosis
#11
Ioana Streata, January Weiner, Marco Iannaccone, Gayle McEwen, Marius Sorin Ciontea, Marian Olaru, Rosanna Capparelli, Mihai Ioana, Stefan H E Kaufmann, Anca Dorhoi
[This corrects the article DOI: 10.1371/journal.pone.0163662.].
2016: PloS One
https://www.readbyqxmd.com/read/27777981/extrapulmonary-aspergillus-infection-in-patients-with-card9-deficiency
#12
Nikolaus Rieber, Roel P Gazendam, Alexandra F Freeman, Amy P Hsu, Amanda L Collar, Janyce A Sugui, Rebecca A Drummond, Chokechai Rongkavilit, Kevin Hoffman, Carolyn Henderson, Lily Clark, Markus Mezger, Muthulekha Swamydas, Maik Engeholm, Rebecca Schüle, Bettina Neumayer, Frank Ebel, Constantinos M Mikelis, Stefania Pittaluga, Vinod K Prasad, Anurag Singh, Joshua D Milner, Kelli W Williams, Jean K Lim, Kyung J Kwon-Chung, Steven M Holland, Dominik Hartl, Taco W Kuijpers, Michail S Lionakis
Invasive pulmonary aspergillosis is a life-threatening mycosis that only affects patients with immunosuppression, chemotherapy-induced neutropenia, transplantation, or congenital immunodeficiency. We studied the clinical, genetic, histological, and immunological features of 2 unrelated patients without known immunodeficiency who developed extrapulmonary invasive aspergillosis at the ages of 8 and 18. One patient died at age 12 with progressive intra-abdominal aspergillosis. The other patient had presented with intra-abdominal candidiasis at age 9, and developed central nervous system aspergillosis at age 18 and intra-abdominal aspergillosis at age 25...
October 20, 2016: JCI Insight
https://www.readbyqxmd.com/read/27777084/crosstalk-between-the-gut-and-the-liver-via-susceptibility-loci-novel-advances-in-inflammatory-bowel-disease-and-autoimmune-liver-disease
#13
REVIEW
Xinyang Li, Jun Shen, Zhihua Ran
Inflammatory bowel disease (IBD) is an autoimmune disorder characterized by chronic, relapsing intestinal inflammation. Autoimmune liver disease (AILD) may be involved in IBD as an extra-intestinal manifestation (EIM). Epidemiologic and anatomic evidence have demonstrated an intimate crosstalk between the gut and the liver. In this review, we briefly introduced nine groups of susceptibility loci shared by inflammatory bowel and autoimmune liver disease for the first time. The genome-wide association studies (GWAS) evidence of pathways involving crosstalk between the gut and the liver is clarified and explained...
October 21, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27684065/the-card9-polymorphisms-rs4077515-rs10870077-and-rs10781499-are-uncoupled-from-susceptibility-to-and-severity-of-pulmonary-tuberculosis
#14
Ioana Streata, January Weiner, Marco Iannaconne, Gayle McEwen, Marius Sorin Ciontea, Marian Olaru, Rosanna Capparelli, Mihai Ioana, Stefan H E Kaufmann, Anca Dorhoi
Genetic variants in the CARD9 gene predispose to inflammatory disorders and chronic infectious diseases. Tuberculosis (TB), a chronic infectious disease affecting the lung, is lethal in Card9-deficient mice. We hypothesized that polymorphisms in the CARD9 gene influence TB progression and disease-associated lung damage in humans. We tested genotype distributions of the CARD9 polymorphisms rs4077515, rs10781499 and rs10870077 in TB patients and healthy subjects in a Caucasian cohort. SNPs were in linkage disequilibrium and none of the haplotypes was significantly enriched in the TB group...
2016: PloS One
https://www.readbyqxmd.com/read/27670879/card9-negatively-regulates-nlrp3-induced-il-1%C3%AE-production-on-salmonella-infection-of-macrophages
#15
Milton Pereira, Panagiotis Tourlomousis, John Wright, Tom P Monie, Clare E Bryant
Interleukin-1β (IL-1β) is a proinflammatory cytokine required for host control of bacterial infections, and its production must be tightly regulated to prevent excessive inflammation. Here we show that caspase recruitment domain-containing protein 9 (CARD9), a protein associated with induction of proinflammatory cytokines by fungi, has a negative role on IL-1β production during bacterial infection. Specifically, in response to activation of the nucleotide oligomerization domain receptor pyrin-domain containing protein 3 (NLRP3) by Salmonella infection, CARD9 negatively regulates IL-1β by fine-tuning pro-IL-1β expression, spleen tyrosine kinase (SYK)-mediated NLRP3 activation and repressing inflammasome-associated caspase-8 activity...
September 27, 2016: Nature Communications
https://www.readbyqxmd.com/read/27558332/tyrosine-kinase-signaling-pathways-in-neutrophils
#16
REVIEW
Krisztina Futosi, Attila Mócsai
Neutrophils play a critical role in antimicrobial host defense, but their improper activation also contributes to inflammation-induced tissue damage. Therefore, understanding neutrophil biology is important for the understanding, diagnosis, and therapy of both infectious and inflammatory diseases. Neutrophils express a large number of cell-surface receptors that sense extracellular cues and trigger various functional responses through complex intracellular signaling pathways. During the last several years, we and others have shown that tyrosine kinases play a critical role in those processes...
September 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27542117/myd88-shapes-vaccine-immunity-by-extrinsically-regulating-survival-of-cd4-t-cells-during-the-contraction-phase
#17
Huafeng Wang, Mengyi Li, Chiung Yu Hung, Meenal Sinha, Linda M Lee, Darin L Wiesner, Vanessa LeBert, Tassanee Lerksuthirat, Kevin Galles, Marulasiddappa Suresh, Anthony L DeFranco, Clifford A Lowell, Bruce S Klein, Marcel Wüthrich
Soaring rates of systemic fungal infections worldwide underscore the need for vaccine prevention. An understanding of the elements that promote vaccine immunity is essential. We previously reported that Th17 cells are required for vaccine immunity to the systemic dimorphic fungi of North America, and that Card9 and MyD88 signaling are required for the development of protective Th17 cells. Herein, we investigated where, when and how MyD88 regulates T cell development. We uncovered a novel mechanism in which MyD88 extrinsically regulates the survival of activated T cells during the contraction phase and in the absence of inflammation, but is dispensable for the expansion and differentiation of the cells...
August 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27456474/subcutaneous-phaeohyphomycosis-caused-by-exophiala-spinifera-in-a-european-patient-with-lymphoma-a-rare-occurrence-case-report-and-literature-review
#18
REVIEW
G Bohelay, S Robert, C Bouges-Michel, M Gerin, A Levy, O Fain, F Caux
Exophiala spinifera is a dematiaceous fungus responsible for rare skin infections presenting as phaeohyphomycosis or chromoblastomycosis which has been primarily reported in tropical and subtropical areas (Asia, South and North America). We report the first case of E. spinifera phaeohyphomycosis in a European patient. The phaeohyphomycosis was limited to the skin, involving the finger of an immunocompromised patient presenting with a large B-cell lymphoma treated by R-mini-CHOP regimen. Remission was initially achieved by surgical excision; however, a local subcutaneous relapse required treatment with itraconazole...
November 2016: Mycoses
https://www.readbyqxmd.com/read/27421992/impairment-of-immune-response-against-dematiaceous-fungi-in-card9-knockout-mice
#19
Weiwei Wu, Ruijun Zhang, Xiaowen Wang, Yinggai Song, Zhengyang Liu, Wenling Han, Ruoyu Li
Dematiaceous fungi are a large group of pathogens that can cause a wide range of diseases in both immunocompetent and immunocompromised hosts. Based on our previous finding of caspase recruitment domain-containing protein 9 (CARD9) mutations in patients with subcutaneous phaeohyphomycosis caused by Phialophora verrucosa (P. verrucosa), we further investigated the exact role of CARD9 in the pathogenesis of phaeohyphomycosis using Card9 knockout (Card9 KO) mice. We showed that Card9 KO mice are profoundly susceptible to P...
October 2016: Mycopathologia
https://www.readbyqxmd.com/read/27363694/polymorphisms-in-the-pattern-recognition-receptor-mincle-gene-clec4e-and-association-with-tuberculosis
#20
Nicholas Bowker, Muneeb Salie, Haiko Schurz, Paul D van Helden, Craig J Kinnear, Eileen G Hoal, Marlo Möller
The mechanisms involved in interactions between Mycobacterium tuberculosis and host innate immune cells determine outcome. Antigen-presenting cells, including macrophages and dendritic cells, express many pattern recognition receptors to identify pathogen-associated molecular patterns, thereby initiating an immune response. A major mycobacterial virulence factor, trehalose-6',6-dimycolate, is recognised by the macrophage-inducible C-type lectin, Mincle, which leads to the activation of the Syk-Card9 signalling pathway in macrophages...
October 2016: Lung
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