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https://www.readbyqxmd.com/read/29915598/the-interaction-of-human-pathogenic-fungi-with-c-type-lectin-receptors
#1
REVIEW
Surabhi Goyal, Juan Camilo Castrillón-Betancur, Esther Klaile, Hortense Slevogt
Fungi, usually present as commensals, are a major cause of opportunistic infections in immunocompromised patients. Such infections, if not diagnosed or treated properly, can prove fatal. However, in most cases healthy individuals are able to avert the fungal attacks by mounting proper antifungal immune responses. Among the pattern recognition receptors (PRRs), C-type lectin receptors (CLRs) are the major players in antifungal immunity. CLRs can recognize carbohydrate ligands, such as β-glucans and mannans, which are mainly found on fungal cell surfaces...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29876879/the-mycobacterial-adjuvant-analogue-tdb-attenuates-neuroinflammation-via-mincle-independent-plc-%C3%AE-1-pkc-erk-signaling-and-microglial-polarization
#2
Mahendravarman Mohanraj, Ponarulselvam Sekar, Horng-Huei Liou, Shwu-Fen Chang, Wan-Wan Lin
Microglial activation has long been recognized as a hallmark of neuroinflammation. Recently, the bacillus Calmette-Guerin (BCG) vaccine has been reported to exert neuroprotective effects against several neurodegenerative disorders. Trehalose-6,6'-dibehenate (TDB) is a synthetic analogue of trehalose-6,6'-dimycolate (TDM, also known as the mycobacterial cord factor) and is a new adjuvant of tuberculosis subunit vaccine currently in clinical trials. Both TDM and TDB can activate macrophages and dendritic cells through binding to C-type lectin receptor Mincle; however, its action mechanism in microglia and their relationship with neuroinflammation are still unknown...
June 6, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29781274/the-synthesis-of-branched-trehalose-glycolipids-and-their-mincle-agonist-activity
#3
Jessie H Bird, Ashna A Khan, Naoya Nishimura, Sho Yamasaki, Mattie S M Timmer, Bridget L Stocker
The macrophage inducible C-type lectin (Mincle) is a pattern recognition receptor that recognises trehalose dimycolate (TDM), and trehalose dibehenate (TDB) and related trehalose diesters, and thus represents a promising target for the development of vaccine adjuvants based on the trehalose glycolipid scaffold. To this end, we report on the synthesis of a series of long-chain α-branched, β-modified trehalose monoesters and diesters to explore how glycolipid structure affects signalling through Mincle. Key steps in our synthetic strategy include a Fráter-Seebach α-alkylation to install the C20 aliphatic lipid on a malic acid derivative, and the formation of a β, γ-epoxide as an intermediate from which modifications to the β-position of the lipid can be made...
May 21, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29726997/mincle-20-years-of-a-versatile-sensor-of-insults
#4
Xiuyuan Lu, Masahiro Nagata, Sho Yamasaki
Macrophage-inducible C-type lectin, better known as Mincle, is a member of the C-type lectin receptor family and is encoded by Clec4e. Mincle was an orphan receptor for a long time after having been discovered as a lipopolysaccharide-induced protein, yet later an adjuvant glycolipid in mycobacteria-trehalose dimycolate-was identified as a ligand. Ligands for Mincle were also found existing in bacteria, fungi and even mammals. When confronted with foreign elements, Mincle can recognize characteristic pathogen-associated molecular patterns, mostly glycolipids, from Mycobacterium tuberculosis and other pathogens, and thus induce immune responses against infection...
May 2, 2018: International Immunology
https://www.readbyqxmd.com/read/29725603/stimulation-of-dectin-1-and-dectin-2-during-parenteral-immunization-but-not-mincle-induces-secretory-iga-in-intestinal-mucosa
#5
Alina S Dzharullaeva, Amir I Tukhvatulin, Alina S Erokhova, Alina S Bandelyuk, Nikita B Polyakov, Andrey I Solovyev, Natalia A Nikitenko, Dmitry V Shcheblyakov, Boris S Naroditsky, Denis Y Logunov, Alexander L Gintsburg
Induction of a robust and long-lived mucosal immune response during vaccination is critical to achieve protection against numerous pathogens. However, traditional injected vaccines are generally poor inducers of mucosal immunity. One of the effective strategies to improve vaccine efficacy is incorporation of adjuvant molecules that enhance and polarize adaptive immune reactions. Effects of Syk-coupled lectin receptor agonists as adjuvants to induce mucosal immune reactions during parenteral immunization are not fully studied...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29722096/the-14th-international-workshops-on-opportunistic-protists-iwop-14
#6
Melanie T Cushion, Andrew H Limper, Aleksey Porollo, Vivian E Saper, Anthony P Sinai, Louis M Weiss
The 14th International Workshops on Opportunistic Protists (IWOP-14) was held August 10-12, 2017 in Cincinnati, OH, USA. The IWOP meetings focus on opportunistic protists (OIs); for example, free-living amoebae, Pneumocystis spp., Cryptosporidium spp., Toxoplasma, the Microsporidia, and kinetoplastid flagellates. The highlights of Pneumocystis spp. research included the reports of primary homothallism for mating; a potential requirement for sexual replication in its life cycle; a new antigen on the surface of small asci; roles for CLRs, Dectin-1, and Mincle in host responses; and identification of MSG families and mechanisms used for surface variation...
May 3, 2018: Journal of Eukaryotic Microbiology
https://www.readbyqxmd.com/read/29693771/a-simple-glycolipid-mimic-of-the-phosphatidylinositol-mannoside-core-from-mycobacterium-tuberculosis-inhibits-macrophage-cytokine-production
#7
Tamim Mosaiab, Sandra Boiteux, Abu Hasanat Md Zulfiker, Ming Q Wei, Milton J Kiefel, Todd A Houston
Glycolipids from Mycobacterium tuberculosis have a profound impact on the innate immune response of the host. Macrophage-inducible C-type lectin (Mincle) is a pattern-recognition receptor that has been shown to bind trehalose dimycolate (TDM) from the mycobacterium and instigate intracellular signalling in the immune cell. There are structural similarities between the structures of TDM and phosphatidyl inositol mannoside (PIM). We thus hypothesized that these latter structures might also modulate an immune response in a similar manner...
April 25, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29675368/mincle-in-the-innate-immune-response-of-mice-fungal-keratitis
#8
Guo-Rong Yu, Jing Lin, Jie Zhang, Cheng-Ye Che, Xu-Dong Peng, Cui Li, Li-Ting Hu, Guo-Qiang Zhu, Kun He, Gui-Qiu Zhao
AIM: To investigate how macrophage inducible C-type lectin (Mincle) influences inflammation in mice fungal keratitis induced by Aspergillus fumigatus ( A. fumigatus ). METHODS: C57BL/6 mice were infected with A. fumigatus after pretreated with Mincle agonist TDB or Mincle neutralizing antibody (MincleAb), taking DMSO or IgG as control group respectively. The cornea lesions were monitored with slit-lamp microscope and evaluated by clinical score. Mincle expression was assessed using reverse transcription-ploymerase chain reaction (RT-PCR) and immunostaining...
2018: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/29643949/high-secretion-of-interleukin-6-and-increased-mincle-receptor-expression-upon-exposure-to-mycobacterial-cord-factor-analog-trehalose-6-6-dibehenate-tdb-in-patients-with-takayasu-arteritis
#9
Nikhil Gupta, Jayakanthan Kabeerdoss, Hindhumathi Mohan, Ruchika Goel, Debashish Danda
Introduction: Suspicion on the association between Takayasu Arteritis (TA) and Tubcerculosis (TB) has been in vogue for years. Prevalence of TB in TA is reported to be higher. We aimed to study innate immune responses in patients with TA on exposure to Trehalose-6,6-dibehenate (TDB), a synthetic analogue of Trehalose-6,6-Dimycolate (TDM, also known as mycobacterial cord factor) in comparison with healthy controls. Materials and Methods: Patients with type V TA, satisfying 1990 ACR criteria, and age and sex matched healthy controls were recruited...
2018: Open Rheumatology Journal
https://www.readbyqxmd.com/read/29599490/interaction-of-glycolipids-with-the-macrophage-surface-receptor-mincle-a-systematic-molecular-dynamics-study
#10
Christian A Söldner, Anselm H C Horn, Heinrich Sticht
Synthetic analogues of mycobacterial trehalose-dimycolate such as trehalose acyl esters have been proposed as novel adjuvants for vaccination. They induce an immune response by binding to the macrophage C-type lectin receptor Mincle. The binding site of trehalose is known, but there is yet only very limited structural information about the binding mode of the acyl esters. Here, we performed a systematic molecular dynamics study of trehalose mono-and diesters with different chain lengths. All acyl chains investigated exhibited a high flexibility and interacted almost exclusively with a hydrophobic groove on Mincle...
March 29, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29541075/overcoming-the-neonatal-limitations-of-inducing-germinal-centers-through-liposome-based-adjuvants-including-c-type-lectin-agonists-trehalose-dibehenate-or-curdlan
#11
Maria Vono, Christiane Sigrid Eberhardt, Elodie Mohr, Floriane Auderset, Dennis Christensen, Mirco Schmolke, Rhea Coler, Andreas Meinke, Peter Andersen, Paul-Henri Lambert, Beatris Mastelic-Gavillet, Claire-Anne Siegrist
Neonates and infants are more vulnerable to infections and show reduced responses to vaccination. Consequently, repeated immunizations are required to induce protection and early life vaccines against major pathogens such as influenza are yet unavailable. Formulating antigens with potent adjuvants, including immunostimulators and delivery systems, is a demonstrated approach to enhance vaccine efficacy. Yet, adjuvants effective in adults may not meet the specific requirements for activating the early life immune system...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29500453/sophora-flavescens-protects-against-mycobacterial-trehalose-dimycolate-induced-lung-granuloma-by-inhibiting-inflammation-and-infiltration-of-macrophages
#12
Dehua Liu, Ben Chung-Lap Chan, Ling Cheng, Miranda Sin-Man Tsang, Jing Zhu, Chun-Wai Wong, Delong Jiao, Helen Yau-Tsz Chan, Ping Chung Leung, Christopher Wai-Kei Lam, Chun Kwok Wong
The immune system responds to Mycobacterium tuberculosis (MTB) infection by forming granulomas to quarantine the bacteria from spreading. Granuloma-mediated inflammation is a cause of lung destruction and disease transmission. Sophora flavescens (SF) has been demonstrated to exhibit bactericidal activities against MTB. However, its immune modulatory activities on MTB-mediated granulomatous inflammation have not been reported. In the present study, we found that flavonoids from Sophora flavescens (FSF) significantly suppressed the pro-inflammatory mediators released from mouse lung alveolar macrophages (MH-S) upon stimulation by trehalose dimycolate (TDM), the most abundant lipoglycan on MTB surface...
March 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29497419/c-type-lectin-like-receptors-as-emerging-orchestrators-of-sterile-inflammation-represent-potential-therapeutic-targets
#13
REVIEW
Elise Chiffoleau
Over the last decade, C-type lectin-like receptors (CTLRs), expressed mostly by myeloid cells, have gained increasing attention for their role in the fine tuning of both innate and adaptive immunity. Not only CTLRs recognize pathogen-derived ligands to protect against infection but also endogenous ligands such as self-carbohydrates, proteins, or lipids to control homeostasis and tissue injury. Interestingly, CTLRs act as antigen-uptake receptors via their carbohydrate-recognition domain for internalization and subsequent presentation to T-cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29482417/microbial-co-infection-alters-macrophage-polarization-phagosomal-escape-and-microbial-killing
#14
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/29401615/differential-susceptibility-of-dectin-1-isoforms-to-functional-inactivation-by-neutrophil-and-fungal-proteases
#15
James S Griffiths, Aiysha Thompson, Matthew Stott, Ankita Benny, Natalie A Lewis, Philip R Taylor, Julian Forton, Sarah Herrick, Selinda J Orr, Eamon P McGreal
Patients with cystic fibrosis (CF) experience chronic or recurrent bacterial and fungal lung infections. Many patients with CF cannot effectively clear Aspergillus from their lungs. This may result in IgE sensitization and the development of allergic bronchopulmonary aspergillosis, or invasive infections, such as Aspergillus bronchitis. Lung disease in patients with CF is associated with neutrophil-dominated inflammation and elevated levels of the serine protease, neutrophil elastase (NE). Various C-type lectin-like receptors (CLRs), including Dectin-1 and Dectin-2, are involved in the immune response to Aspergillus...
January 22, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29400702/integrin-cd11b-negatively-regulates-mincle-induced-signaling-via-the-lyn-sirp%C3%AE-shp1-complex
#16
Quanri Zhang, Wook-Bin Lee, Ji-Seon Kang, Lark Kyun Kim, Young-Joon Kim
During mycobacteria infection, anti-inflammatory responses allow the host to avoid tissue damage caused by overactivation of the immune system; however, little is known about the negative modulators that specifically control mycobacteria-induced immune responses. Here we demonstrate that integrin CD11b is a critical negative regulator of mycobacteria cord factor-induced macrophage-inducible C-type lectin (Mincle) signaling. CD11b deficiency resulted in hyperinflammation following mycobacterial infection. Activation of Mincle by mycobacterial components turns on not only the Syk signaling pathway but also CD11b signaling and induces formation of a Mincle-CD11b signaling complex...
February 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29386115/cd209a-synergizes-with-dectin-2-and-mincle-to-drive-severe-th17-cell-mediated-schistosome-egg-induced-immunopathology
#17
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/29355515/spliceosome-associated-protein-130-exacerbates-alcohol-induced-liver-injury-by-inducing-nlrp3-inflammasome-mediated-il-1%C3%AE-in-mice
#18
Jong-Won Kim, Yoon-Seok Roh, Hyeneui Jeong, Ho-Keun Yi, Min-Ho Lee, Chae-Woong Lim, Bumseok Kim
Excessive alcohol consumption leads to chronic liver diseases. Macrophage-inducible C-type lectin (Mincle) is a C-type lectin receptor that recognizes spliceosome-associated protein 130 (SAP130) known as an endogenous ligand released from dying cells. The aim was to examine the role of Mincle-SAP130 in the pathogenesis of alcoholic liver disease. Alcohol-induced liver injury was induced in wild-type (WT) and Mincle knockout (KO) mice by using a chronic-binge ethanol-feeding model. Mincle KO mice showed significant lower hepatic steatosis, inflammation with neutrophil infiltration, and fibrosis compared with WT mice after alcohol feeding...
April 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29290115/lipidated-brartemicin-analogues-are-potent-th1-stimulating-vaccine-adjuvants
#19
Amy J Foster, Masahiro Nagata, Xiuyuan Lu, Amy T Lynch, Zakaria Omahdi, Eri Ishikawa, Sho Yamasaki, Mattie S M Timmer, Bridget L Stocker
Effective Th1-stimulating vaccine adjuvants typically activate antigen presenting cells (APCs) through pattern recognition receptors (PRRs). Macrophage inducible C-type lectin (Mincle) is a PRR expressed on APCs and has been identified as a target for Th1-stimulating adjuvants. Herein, we report on the synthesis and adjuvanticity of rationally designed brartemicin analogues containing long-chain lipids and demonstrate that they are potent Mincle agonists that activate APCs to produce inflammatory cytokines in a Mincle-dependent fashion...
February 8, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29230225/sensing-lipids-with-mincle-structure-and-function
#20
REVIEW
Spencer J Williams
Mincle is a C-type lectin receptor that has emerged as an important player in innate immunity through its capacity to recognize a wide range of lipidic species derived from damaged/altered self and foreign microorganisms. Self-ligands include sterols (e.g., cholesterol), and β-glucosylceramides, and the protein SAP130, which is released upon cell death. Foreign lipids comprise those from both microbial pathogens and commensals and include glycerol, glucose and trehalose mycolates, and glycosyl diglycerides...
2017: Frontiers in Immunology
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