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MyD88 in T cells

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https://www.readbyqxmd.com/read/29133782/mtor-intersects-antibody-inducing-signals-from-taci-in-marginal-zone-b-cells
#1
Jordi Sintes, Maurizio Gentile, Shuling Zhang, Yolanda Garcia-Carmona, Giuliana Magri, Linda Cassis, Daniel Segura-Garzón, Alessandra Ciociola, Emilie K Grasset, Sabrina Bascones, Laura Comerma, Marc Pybus, David Lligé, Irene Puga, Cindy Gutzeit, Bing He, Wendy DuBois, Marta Crespo, Julio Pascual, Anna Mensa, Juan Ignacio Aróstegui, Manel Juan, Jordi Yagüe, Sergi Serrano, Josep Lloreta, Eric Meffre, Michael Hahne, Charlotte Cunningham-Rundles, Beverly A Mock, Andrea Cerutti
Mechanistic target of rapamycin (mTOR) enhances immunity in addition to orchestrating metabolism. Here we show that mTOR coordinates immunometabolic reconfiguration of marginal zone (MZ) B cells, a pre-activated lymphocyte subset that mounts antibody responses to T-cell-independent antigens through a Toll-like receptor (TLR)-amplified pathway involving transmembrane activator and CAML interactor (TACI). This receptor interacts with mTOR via the TLR adapter MyD88. The resulting mTOR activation instigates MZ B-cell proliferation, immunoglobulin G (IgG) class switching, and plasmablast differentiation through a rapamycin-sensitive pathway that integrates metabolic and antibody-inducing transcription programs, including NF-κB...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29131267/interleukin-33-promotes-the-inflammatory-reaction-in-chronic-rhinosinusitis-with-nasal-polyps-by-nf-%C3%AE%C2%BAb-signaling-pathway
#2
L Zhang, L-L Jiang, Z-W Cao
OBJECTIVE: Interleukin (IL)-33 promotes T helper (Th2) immune response and may be involved in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). Using murine and human specimens, we evaluated the role of IL-33 in CRSwNP. MATERIALS AND METHODS: To establish CRSwNP, Balb/c mice were sensitized with house dust mite, followed up by intranasal exposure to Staphylococcus aureus to stimulate the inflammatory response of nasal mucosa. The hematoxylin-eosin staining and total serum IgE were used to the successful construction of CRSwNP model...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29120744/staphylococcus-aureus-virulent-psm%C3%AE-peptides-induce-keratinocyte-alarmin-release-to-orchestrate-il-17-dependent-skin-inflammation
#3
Seitaro Nakagawa, Masanori Matsumoto, Yuki Katayama, Rena Oguma, Seiichiro Wakabayashi, Tyler Nygaard, Shinobu Saijo, Naohiro Inohara, Michael Otto, Hiroyuki Matsue, Gabriel Núñez, Yuumi Nakamura
Staphylococcus aureus commonly colonizes the epidermis, but the mechanisms by which the host senses virulent, but not commensal, S. aureus to trigger inflammation remain unclear. Using a murine epicutaneous infection model, we found that S. aureus-expressed phenol-soluble modulin (PSM)α, a group of secreted virulence peptides, is required to trigger cutaneous inflammation. PSMα induces the release of keratinocyte IL-1α and IL-36α, and signaling via IL-1R and IL-36R was required for induction of the pro-inflammatory cytokine IL-17...
November 8, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29120743/staphylococcus-aureus-epicutaneous-exposure-drives-skin-inflammation-via-il-36-mediated-t-cell-responses
#4
Haiyun Liu, Nathan K Archer, Carly A Dillen, Yu Wang, Alyssa G Ashbaugh, Roger V Ortines, Tracy Kao, Steven K Lee, Shuting S Cai, Robert J Miller, Mark C Marchitto, Emily Zhang, Daniel P Riggins, Roger D Plaut, Scott Stibitz, Raif S Geha, Lloyd S Miller
Staphylococcus aureus colonization contributes to skin inflammation in diseases such as atopic dermatitis, but the signaling pathways involved are unclear. Herein, epicutaneous S. aureus exposure to mouse skin promoted MyD88-dependent skin inflammation initiated by IL-36, but not IL-1α/β, IL-18, or IL-33. By contrast, an intradermal S. aureus challenge promoted MyD88-dependent host defense initiated by IL-1β rather than IL-36, suggesting that different IL-1 cytokines trigger MyD88 signaling depending on the anatomical depth of S...
November 8, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29119662/toxoplasma-gondii-infection-shifts-dendritic-cells-into-an-amoeboid-rapid-migration-mode-encompassing-podosome-dissolution-secretion-of-timp-1-and-reduced-proteolysis-of-extracellular-matrix
#5
Einar B Ólafsson, Manuel Varas-Godoy, Antonio Barragan
Dendritic cells (DCs) infected by Toxoplasma gondii rapidly acquire a hypermigratory phenotype that promotes systemic parasite dissemination by a 'Trojan horse' mechanism in mice. Recent paradigms of leukocyte migration have identified the amoeboid migration mode of DCs as particularly suited for rapid locomotion in extracellular matrix and tissues. Here, we have developed a microscopy-based high-throughput approach to assess motility and matrix degradation by Toxoplasma-challenged murine and human DCs. DCs challenged with T...
November 8, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/29118245/mer-receptor-tyrosine-kinase-signaling-prevents-self-ligand-sensing-and-aberrant-selection-in-germinal-centers
#6
Stephanie L Schell, Chetna Soni, Melinda J Fasnacht, Phillip P Domeier, Timothy K Cooper, Ziaur S M Rahman
Mer tyrosine kinase (Mer) signaling maintains immune tolerance by clearing apoptotic cells (ACs) and inducing immunoregulatory signals. We previously showed that Mer-deficient mice (Mer(-/-)) have increased germinal center (GC) responses, T cell activation, and AC accumulation within GCs. Accumulated ACs in GCs can undergo necrosis and release self-ligands, which may influence the outcome of a GC response and selection. In this study, we generated Mer(-/-) mice with a global MyD88, TLR7, or TLR9 deficiency and cell type-specific MyD88 deficiency to study the functional correlation between Mer and TLRs in the development of GC responses and autoimmunity...
November 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29108995/cd1d-is-a-novel-cell-surface-marker-for-human-monocytic-myeloid-derived-suppressor-cells-with-t-cell-suppression-activity-in-peripheral-blood-after-allogeneic-hematopoietic-stem-cell-transplantation
#7
Borim An, Ji-Young Lim, Suji Jeong, Dong-Mi Shin, Eun Young Choi, Chang-Ki Min, Seok-Ho Hong
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that regulate immune responses in cancer and various pathological conditions. However, the phenotypic and functional heterogeneity of human MDSCs represents a major hurdle for the development of therapeutic strategies targeting or regulating MDSCs in tumor progression, inflammation, and graft-versus-host disease (GVHD). We previously shown that circulating HLA-DR(-)CD14(+) monocytic MDSCs are a major contributor to clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT)...
November 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29061706/nlrp3-is-a-critical-regulator-of-inflammation-and-innate-immune-cell-response-during-mycoplasma-pneumoniae-infection
#8
Jesus A Segovia, Te-Hung Chang, Vicki T Winter, Jacqueline J Coalson, Marianna P Cagle, Lavanya Pandranki, Santanu Bose, Joel B Baseman, Thirumalai R Kannan
Mycoplasma pneumoniae is an atypical bacterial respiratory pathogen known to cause a range of airway inflammation and lung and extrapulmonary pathologies. We recently reported that an M. pneumoniae-derived ADP-ribosylating and vacuolating toxin called Community-Acquired Respiratory Distress Syndrome (CARDS) toxin is capable of triggering NLRP3 (NLR-family, leucine-rich repeat protein 3) inflammasome activation and interleukin-1β secretion in macrophages. However, it is unclear whether the NLRP3 inflammasome is important for the immune response during M...
October 23, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29055013/a-synthetic-cd8%C3%AE-myd88-co-receptor-enhances-cd8-t-cell-responses-to-weakly-immunogenic-and-lowly-expressed-tumor-antigens
#9
Sabina Kaczanowska, Ann Mary Joseph, Jitao Guo, Alexander K Tsai, Jackline Joy M Lasola, Kenisha Younger, Yuji Zhang, Cruz Velasco Gonzalez, Eduardo Davila
T cell-based immunotherapies are a promising approach for patients with advanced cancers. However, various obstacles limit T cell efficacy, including suboptimal T cell receptor (TCR) activation and an immunosuppressive tumor environment. Here we developed a fusion protein by linking CD8α and MyD88 (CD8α:MyD88) to enhance CD8+ T cell responses to weakly immunogenic and poorly expressed tumor antigens. CD8α:MyD88-engineered T cells exhibited increased proliferation and expression of effector and co-stimulatory molecules in a tumor antigen-dependent manner...
October 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/29040945/quercetin-protects-mouse-liver-against-triptolide-induced-hepatic-injury-by-restoring-th17-treg-balance-through-tim-3-and-tlr4-myd88-nf-%C3%AE%C2%BAb-pathway
#10
Cai-Bing Wei, Kun Tao, Rong Jiang, Lian-Di Zhou, Qi-Hui Zhang, Chun-Su Yuan
Triptolide (TP) is a diterpene triepoxide with various biological activities, but its clinical applications have been limited by potential hepatotoxicity, which can be attributed to T helper 17 (Th17)/T regulatory (Treg) cell imbalance. Quercetin (QE), a natural flavonoid, has been reported to have many benefits and medicinal properties, including hepatoprotective activity against TP-induced liver injury. However, the hepatoprotection mechanisms have not been clarified. The present study was designed to explore the protective effect and the mechanism of QE against TP-induced liver injury...
October 14, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29036979/-role-of-ash2-absent-small-or-homeotic-like-and-jumonji-domain-containing-protein-3-on-histone-methylation-of-interferon-gamma-gene-and-their-associations-with-vascular-damage-of-kawasaki-disease
#11
J H Mei, G Tang, Q Wang, P Q Wen, M G Xu, D Cui, D L Ma, C Liu, G B Wang
Objective: To investigate the impacts of ash2 (absent, small, or homeotic)-like (Ash2L) and Jumonji domain-containing protein 3 (Jmjd3) on histone methylation of interferon-gamma(IFN-γ) gene and association with vascular damage of Kawasaki disease (KD) in acute phase. Methods: This study was performed among 36 children with KD in acute phase (KD group) and 28 age-matched health children (control group), who were treated or underwent physical examination in our hospital between February 2015 and June 2016. Patients were further divided into KD groups with or without coronary artery lesions (KD-CAL(+) , 16 cases; KD-CAL(-), 20 cases)...
September 24, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/29036304/il-1r-and-myd88-signaling-in-cd4-t-cells-promote-th17-immunity-and-atherosclerosis
#12
Daniel Engelbertsen, Sara Rattik, Maria Wigren, Jenifer Vallejo, Goran Marinkovic, Alexandru Schiopu, Harry Björkbacka, Jan Nilsson, Eva Bengtsson
Aims: The role of CD4+ T cells in atherosclerosis has been shown to be dependent on cytokine cues that regulate lineage commitment into mature T helper subsets. In this study we tested the roles of IL-1R1 and MyD88 signaling in CD4+ T cells in atherosclerosis. Methods and results: We transferred apoe-/-myd88+/+or apoe-/-myd88-/- CD4+ T cells to T- and B-cell-deficient rag1-/-apoe-/- mice fed high fat diet. Mice given apoe-/-myd88-/- CD4+ T cells exhibited reduced atherosclerosis compared to mice given apoe-/-myd88+/+ CD4+ T cells...
September 28, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29026137/opiate-use-inhibits-tlr9-signaling-pathway-in-vivo-possible-role-in-pathogenesis-of-hiv-1-infection
#13
Yanyan Liao, Junjun Jiang, Bingyu Liang, Fumei Wei, Jiegang Huang, Peijiang Pan, Jinming Su, Bo Zhou, Ning Zang, Li Ye, Hao Liang
The molecular mechanism of opiate use promoting HIV-1 infection is not fully understood. TLR9 is expressed in many immune cells, including monocytes, macrophages, which can recognize viruses and viral products and consequently induce the production of antiviral factors and initiate immune responses. Previous studies have shown that chronic viral infections can overcome and impair TLR9 pathway. We aimed to explore whether opiate use enhances HIV infection through inhibition of TLR9 pathway via a population-based study...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29022493/immunonutrition-before-esophagectomy-impact-on-immune-surveillance-mechanisms
#14
Marco Scarpa, Andromachi Kotsafti, Matteo Fassan, Melania Scarpa, Francesco Cavallin, Teresa Nardi, Eleonora Pinto, Rita Alfieri, Matteo Cagol, Marco Agostini, Massimo Rugge, Ignazio Castagliuolo, Carlo Castoro
Preoperative oral immunonutrition was demonstrated to improve immune response and to decrease the infection rate in patients with cancer. This study aimed to assess how immunonutrition could influence the immune cell response in the mucosal microenvironment of esophageal adenocarcinoma. Therefore, A prospective cohort of consecutive patients undergoing esophagectomy for esophageal adenocarcinoma was enrolled. A subgroup of them was given preoperative oral immunonutrition with Oral Impact® and was compared to those who received no preoperative supplementation...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28982539/treponema-pallidum-flagellins-stimulate-mmp-9-and-mmp-13-expression-via-tlr5-and-mapk-nf-%C3%AE%C2%BAb-signaling-pathways-in-human-epidermal-keratinocytes
#15
Chuanhao Jiang, Man Xu, Xingxing Kuang, Jinhong Xiao, Manyi Tan, Yafeng Xie, Yongjian Xiao, Feijun Zhao, Yimou Wu
Syphilis is a chronic disease caused by Treponema pallidum and the pathogenesis is still unclear. T. pallidum infection induced inflammatory responses are involved in the immunopathological damage in skin and other tissues. Flagellin, the monomeric subunit of bacterial flagella, is a classic pathogen associated molecular patterns (PAMPs) that interacts to TLR5 and induces inflammatory responses. Keratinocytes, as immune sentinels recognize the PAMPs via TLRs, play an important role in skin innate immune response...
October 2, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28962218/effects-of-tim-3-silencing-on-the-viability-of-fibroblast-like-synoviocytes-and-lipopolysaccharide-induced-inflammatory-reactions
#16
Rui Wu, Li Long, Qiqi Chen, Xiaodan Wu, Jing Zhu, Bin Zhou, Jia Cheng
The objective of the present study was to investigate the effects of Tim-3 silencing on cell viability and lipopolysaccharide (LPS)-induced inflammatory reactions in fibroblast-like synoviocytes (FLS). T-cell immunoglobulin mucin domain molecule (Tim)-3 expression in FLS obtained from patients with rheumatoid arthritis (RA) and normal controls were detected by western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). Small interfering (si)RNA was transfected using Lipofectamine(®) 2000 to decrease Tim-3 expression...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28903575/diagnostic-tools-of-waldenstr%C3%A3-ms-macroglobulinemia-best-possibilities-for-non-invasive-and-long-term-disease-monitoring
#17
K Growkova, Z Kufová, T Sevcikova, J Filipová, M Kascak, T Jelínek, S Grosicki, A Barchnicka, Ľ Roziaková, M Mistrík, M Simicek, R Hájek
Waldenströms macroglobulinemia (WM) is a B-cell malignancy characterized by high level of monoclonal immunoglobulin M (IgM) paraprotein in blood serum and associated with the bone marrow infiltration by malignant cells with lymphoplasmacytic differentiation. WM remains incurable advances in therapy. Most of WM cases are associated with a somatic point mutation L265P in MYD88. Significantly higher risk of progression from the IgM monoclonal gammopathy of undetermined significance (IgM MGUS) to WM for patients with mutated MYD88 gene suggests that this mutation is an early oncogenic event and plays a central role in development of malignant clones...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28899983/regulatory-nk-cells-mediated-between-immunosuppressive-monocytes-and-dysfunctional-t-cells-in-chronic-hbv-infection
#18
Haijun Li, Naicui Zhai, Zhongfeng Wang, Hongxiao Song, Yang Yang, An Cui, Tianyang Li, Guangyi Wang, Junqi Niu, Ian Nicholas Crispe, Lishan Su, Zhengkun Tu
BACKGROUND AND AIMS: HBV infection represents a major health problem worldwide, but the immunological mechanisms by which HBV causes chronic persistent infection remain only partly understood. Recently, cell subsets with suppressive features have been recognised among monocytes and natural killer (NK) cells. Here we examine the effects of HBV on monocytes and NK cells. METHODS: Monocytes and NK cells derived from chronic HBV-infected patients and healthy controls were purified and characterised for phenotype, gene expression and cytokines secretion by flow cytometry, quantitative real-time (qRT)-PCR, ELISA and western blotting...
September 12, 2017: Gut
https://www.readbyqxmd.com/read/28895840/crucial-role-for-t-cell-intrinsic-il-18r-myd88-signaling-in-cognate-immune-response-to-intracellular-parasite-infection
#19
Ana-Carolina Oliveira, João Francisco Gomes-Neto, Carlos-Henrique Dantas Barbosa, Alessandra Granato, Bernardo S Reis, Bruno Maia Santos, Rita Fucs, Fábio B Canto, Helder I Nakaya, Alberto Nóbrega, Maria Bellio
MyD88 is the main adaptor molecule for TLR and IL-1R family members. Here, we demonstrated that T-cell intrinsic MyD88 signaling is required for proliferation, protection from apoptosis and expression of activation/memory genes during infection with the intracellular parasite Trypanosoma cruzi, as evidenced by transcriptome and cytometry analyses in mixed bone-marrow (BM) chimeras. The lack of direct IL-18R signaling in T cells, but not of IL-1R, phenocopied the absence of the MyD88 pathway, indicating that IL-18R is a critical MyD88-upstream pathway involved in the establishment of the Th1 response against an in vivo infection, a presently controvert subject...
September 12, 2017: ELife
https://www.readbyqxmd.com/read/28887852/cd8-lineage-dendritic-cells-determine-adaptive-immune-responses-to-inflammasome-activation-upon-sterile-skin-injury
#20
Rituparna Chakraborty, Janin Chandra, Shuai Cui, Lynn Tolley, Matthew A Cooper, Mark Kendall, Ian H Frazer
The molecular links between sterile inflammation and induction of adaptive immunity have not been fully identified. Here, we examine how damage associated molecular patterns (DAMPs), as opposed to pathogen associated molecules (PAMPs), regulates the immune response to non-self-antigens presented at the site of the physical injury. Heat applied briefly to the skin invokes sterile inflammation, characterised by local cell death and caspase-1 activation without demonstrably disrupting skin integrity. Co-delivery of ovalbumin (OVA) with heat injury induces OVA-specific CD8(+) T cell responses and this is dependent on caspase-1 activation and MyD88 signalling...
September 8, 2017: Experimental Dermatology
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