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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
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...
2016: Nature Communications
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
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
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
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
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
M Mansour Ceesay, Shahram Kordasti, Eamaan Rufaie, Nicholas Lea, Melvyn Smith, Jim Wade, Abdel Douiri, Ghulam J Mufti, Antonio Pagliuca
BACKGROUND: Invasive fungal disease (IFD) is a disease of immunocompromised hosts. Cytokines are important mediators of innate and adaptive immune system. The aim of this study was to identify cytokine profiles that correlate with increased risk of IFD. METHODS: We prospectively enrolled 172 adult haematology patients undergoing intensive chemotherapy, immunosuppressive therapy, and haematopoietic stem cell transplantation. Pro-inflammatory cytokine profiling using 30-plex Luminex assay was performed at baseline and during treatment...
September 2016: Journal of Infection
B Pilmis, A Puel, O Lortholary, F Lanternier
Incidence of invasive fungal infections increases over time with the rise in at-risk populations; in particular, patients with acquired immunodeficiencies due to immunosuppressive therapies such as anti-tumour necrosis factor-α (TNF-α) treatment, cirrhosis or burns. Some primary immunodeficiencies (PID) can also predispose selectively to invasive fungal diseases. Conversely, some atypical fungal diseases can reveal new PID. Deep dermatophytosis, Candida central nervous system infections or gastrointestinal disease, or disseminated phaeohyphomycosis-revealed CARD9 deficiency...
August 2016: Clinical Microbiology and Infection
Behdad Navabi, Julia Elizabeth Mainwaring Upton
BACKGROUND: Eosinophilia is not an uncommon clinical finding. However, diagnosis of its cause can be a dilemma once common culprits, namely infection, allergy and reactive causes are excluded. Primary immunodeficiency disorders (PID) are among known differentials of eosinophilia. However, the list of PIDs typically reported with eosinophilia is small and the literature lacks an inclusive list of PIDs which have been reported with eosinophilia. This motivated us to review the literature for all PIDs which have been described to have elevated eosinophils as this may contribute to an earlier diagnosis of PID and further the understanding of eosinophilia...
2016: Allergy, Asthma, and Clinical Immunology
Charlotte Ridler
No abstract text is available yet for this article.
June 2016: Nature Reviews. Gastroenterology & Hepatology
Bruno Lamas, Mathias L Richard, Valentin Leducq, Hang-Phuong Pham, Marie-Laure Michel, Gregory Da Costa, Chantal Bridonneau, Sarah Jegou, Thomas W Hoffmann, Jane M Natividad, Loic Brot, Soraya Taleb, Aurélie Couturier-Maillard, Isabelle Nion-Larmurier, Fatiha Merabtene, Philippe Seksik, Anne Bourrier, Jacques Cosnes, Bernhard Ryffel, Laurent Beaugerie, Jean-Marie Launay, Philippe Langella, Ramnik J Xavier, Harry Sokol
Complex interactions between the host and the gut microbiota govern intestinal homeostasis but remain poorly understood. Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. CARD9 promotes recovery from colitis by promoting interleukin (IL)-22 production, and Card9(-/-) mice are more susceptible to colitis. The microbiota is altered in Card9(-/-) mice, and transfer of the microbiota from Card9(-/-) to wild-type, germ-free recipients increases their susceptibility to colitis...
June 2016: Nature Medicine
Ana Karina Alves de Medeiros, Evelyn Lodewick, Delfien J A Bogaert, Filomeen Haerynck, Sabine Van Daele, Bart Lambrecht, Sara Bosma, Laure Vanderdonckt, Olivier Lortholary, Mélanie Migaud, Jean-Laurent Casanova, Anne Puel, Fanny Lanternier, Jo Lambert, Lieve Brochez, Melissa Dullaers
No abstract text is available yet for this article.
April 26, 2016: Journal of Clinical Immunology
Rebecca A Drummond, Michail S Lionakis
Human CARD9 deficiency is an autosomal recessive primary immunodeficiency disorder caused by biallelic mutations in the gene CARD9, which encodes a signaling protein that is found downstream of many C-type lectin receptors (CLRs). CLRs encompass a large family of innate recognition receptors, expressed predominantly by myeloid and epithelial cells, which bind fungal carbohydrates and initiate antifungal immune responses. Accordingly, human CARD9 deficiency is associated with the spontaneous development of persistent and severe fungal infections that primarily localize to the skin and subcutaneous tissue, mucosal surfaces and/or central nervous system (CNS)...
2016: Frontiers in Cellular and Infection Microbiology
A Heinrich, K A Heyl, E Klaile, M M Müller, T E Klassert, A Wiessner, K Fischer, R R Schumann, U Seifert, K Riesbeck, A Moter, B B Singer, S Bachmann, H Slevogt
The human restricted pathogen Moraxella catarrhalis is an important causal agent for exacerbations in chronic obstructive lung disease (COPD) in adults. In such patients, increased numbers of granulocytes are present in the airways, which correlate with bacteria-induced exacerbations and severity of the disease. Our study investigated whether the interaction of M. catarrhalis with the human granulocyte-specific carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-3 is linked to NF-κB activation, resulting in chemokine production...
March 31, 2016: Cellular Microbiology
Tamás Németh, Krisztina Futosi, Cassian Sitaru, Jürgen Ruland, Attila Mócsai
Neutrophils are terminally differentiated cells with limited transcriptional activity. The biological function of their gene expression changes is poorly understood. CARD9 regulates transcription during antifungal immunity but its role in sterile inflammation is unclear. Here we show that neutrophil CARD9 mediates pro-inflammatory chemokine/cytokine but not lipid mediator release during non-infectious inflammation. Genetic deficiency of CARD9 suppresses autoantibody-induced arthritis and dermatitis in mice...
2016: Nature Communications
Xun Li, Xavier Cullere, Hiroshi Nishi, Gurpanna Saggu, Enrique Durand, Michael K Mansour, Jenny M Tam, Xiu-Yu Song, Xin Lin, Jatin M Vyas, Tanya Mayadas
The C-type lectin receptor dectin-1 and the integrin Mac-1 have key roles in controlling fungal infection. Here, we demonstrate that dectin-1- and Mac-1-induced activation of protein kinase Cδ in neutrophils, independent of the Card9 adaptor, is required for reactive oxygen species production and for intracellular killing upon Candida albicans uptake. Protein kinase Cδ was also required for zymosan-induced cytokine generation in neutrophils. In macrophages, protein kinase Cδ deficiency prevented fungi-induced reactive oxygen species generation but had no effect on activation of TGF-β-activated kinase-1, an effector of Card9, or nuclear factor κB activation, nor did it affect phagolysosomal maturation, autophagy, or intracellular C...
September 2016: Journal of Leukocyte Biology
Ana Karina Alves de Medeiros, Evelyn Lodewick, Delfien J A Bogaert, Filomeen Haerynck, Sabine Van Daele, Bart Lambrecht, Sara Bosma, Laure Vanderdonckt, Olivier Lortholary, Mélanie Migaud, Jean-Laurent Casanova, Anne Puel, Fanny Lanternier, Jo Lambert, Lieve Brochez, Melissa Dullaers
Chronic mucocutaneous or invasive fungal infections are generally the result of primary or secondary immune dysfunction. Patients with autosomal recessive CARD9 mutations are also predisposed to recurrent mucocutaneous and invasive fungal infections with Candida spp., dermatophytes (e.g., Trichophyton spp.) and phaeohyphomycetes (Exophiala spp., Phialophora verrucosa). We study a consanguineous family of Turkish origin in which three members present with distinct clinical phenotypes of chronic mucocutaneous and invasive fungal infections, ranging from chronic mucocutaneous candidiasis (CMC) in one patient, treatment-resistant cutaneous dermatophytosis and deep dermatophytosis in a second patient, to CMC with Candida encephalitis and endocrinopathy in a third patient...
April 2016: Journal of Clinical Immunology
Hongqing Li, Zhonghao Tang, Huili Zhu, Haiyan Ge, Shilei Cui, Weiping Jiang
BACKGROUND: Lung adenocarcinoma can easily cause malignant pleural effusion which was difficult to discriminate from benign pleural effusion. Now there was no biomarker with high sensitivity and specificity for the malignant pleural effusion. PURPOSE: This study used proteomics technology to acquire and analyze the protein profiles of the benign and malignant pleural effusion, to seek useful protein biomarkers with diagnostic value and to establish the diagnostic model...
June 2016: Journal of Cancer Research and Clinical Oncology
Nicholas Jones, Tomaz Garcez, William Newman, David Denning
A 25-year-old woman presented with unilateral red eye and visual blur, and was found to have panuveitis with an inflammatory white mass at the macula, initially presumed to be Toxoplasma retinitis. After failure to respond, she underwent vitrectomy, which produced Candida albicans. Despite intraocular and systemic antifungal treatment, she lost all vision in that eye. Two years later, she developed unilateral hip osteomyelitis leading to total hip replacement and also revealing Candida infection. By clinical exome sequencing, she was then found to have caspase recruitment domain 9 (CARD9) deficiency, an autosomal recessive disorder that causes a specific susceptibility to candidal infections...
2016: BMJ Case Reports
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