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https://www.readbyqxmd.com/read/28315386/card9-mediated-ambient-pm2-5-induced-pulmonary-injury-is-associated-with-th17-cell
#1
Shuo Jiang, Liang Bo, Xihao Du, Jie Liu, Xuejiao Zeng, Guanglong He, Qinghua Sun, Haidong Kan, Weimin Song, Yuquan Xie, Jinzhuo Zhao
Inflammation and oxidative stress are important risk factors in PM2.5-induced injury. The current study attempted to study the role of caspase recruitment domain (CARD) 9 in ambient PM2.5-induced pulmonary injury in mice. The CARD9(-/-) and C57BL/6 mice were exposed to 3.6, 7.8 and 15.6mg/kg.bw of PM2.5 or saline by intratracheal instillation. After the last PM2.5 exposure, the spleen, bronchoalveolar lavage fluid (BALF) and pulmonary tissue were collected and examined. The results showed that PM2.5 exposure induced inflammatory cell infiltration and alveolar septal thickening in the lung...
March 14, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28295265/card9-controls-dectin-1-induced-t-cell-cytotoxicity-and-tumor-growth-in-mice
#2
Haas Tobias, Heidegger Simon, Wintges Alexander, Bscheider Michael, Bek Sarah, Fischer Julius C, Eisenkolb Gabriel, Schmickl Martina, Spoerl Silvia, Peschel Christian, Poeck Hendrik, Ruland Jürgen
Activation of the C-type lectin receptor Dectin-1 by β-glucans triggers multiple signals within dendritic cells (DCs) that result in activation of innate immunity. While these mechanisms can potently prime CD8(+) cytotoxic T cell (CTL) responses without additional adjuvants, the Dectin-1 effector pathways that control CTL induction remain unclear. Here we demonstrate that Dectin-1-induced CTL cross-priming in mice does not require inflammasome activation but strictly depends on the adapter protein Card9 in vitro...
March 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28266741/signaling-and-targeted-therapy-of-inflammatory-cells-in-epidermolysis-bullosa-acquisita
#3
REVIEW
Ralf J Ludwig
Pemphigoid diseases (PD) are chronic and life-threating autoimmune diseases of the skin and mucous membranes. PD are characterized and caused by autoantibodies targeting components of the basement membrane. In the PD epidermolysis bullosa acquisita (EBA) the target autoantigen is type VII collagen. Current treatment options of PD, especially EBA, are limited and are mostly based on systemic immunosuppression. Animal models of PD have greatly advanced our understanding of PD pathogenesis. This has led to the identification of several novel therapeutic targets, including signaling molecules...
March 7, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28217370/tryptophan-a-gut-microbiota-derived-metabolites-regulating-inflammation
#4
REVIEW
Lucie Etienne-Mesmin, Benoit Chassaing, Andrew T Gewirtz
Inflammatory bowel diseases (IBD), which comprise Crohn's disease and ulcerative colitis, are chronic intestinal disorders with an increased prevalence and incidence over the last decade in many different regions over the world. The etiology of IBD is still not well defined, but evidence suggest that it results from perturbation of the homeostasis between the intestinal microbiota and the mucosal immune system, with the involvement of both genetic and environmental factors. Genome wide association studies, which involve large-scale genome-wide screening of potential polymorphism, have identified several mutations associated with IBD...
February 6, 2017: World Journal of Gastrointestinal Pharmacology and Therapeutics
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
#5
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
#6
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
#7
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...
March 1, 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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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...
February 2017: 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
#18
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
#19
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
#20
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
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