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MyD88 in T cells

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https://www.readbyqxmd.com/read/29348435/macrophage-sensing-of-single-walled-carbon-nanotubes-via-toll-like-receptors
#1
Sourav P Mukherjee, Olesja Bondarenko, Pekka Kohonen, Fernando T Andón, Táňa Brzicová, Isabel Gessner, Sanjay Mathur, Massimo Bottini, Paolo Calligari, Lorenzo Stella, Elena Kisin, Anna Shvedova, Reija Autio, Heli Salminen-Mankonen, Riitta Lahesmaa, Bengt Fadeel
Carbon-based nanomaterials including carbon nanotubes (CNTs) have been shown to trigger inflammation. However, how these materials are 'sensed' by immune cells is not known. Here we compared the effects of two carbon-based nanomaterials, single-walled CNTs (SWCNTs) and graphene oxide (GO), on primary human monocyte-derived macrophages. Genome-wide transcriptomics assessment was performed at sub-cytotoxic doses. Pathway analysis of the microarray data revealed pronounced effects on chemokine-encoding genes in macrophages exposed to SWCNTs, but not in response to GO, and these results were validated by multiplex array-based cytokine and chemokine profiling...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343453/polygonatum-sibiricum-polysaccharides-play-anti-cancer-effect-through-tlr4-mapk-nf-%C3%AE%C2%BAb-signaling-pathways
#2
Tingting Long, Zijing Liu, Jingchuan Shang, Xing Zhou, Shuang Yu, Hui Tian, Yixi Bao
OBJECTIVE: To investigate the anti-cancer effect of Polygonatum sibiricum polysaccharides (PSP) and the underlying mechanism. METHODS: Tumor-bearing mice were randomly divided into normal saline (NS) group, adriamycin (ADM) group, PSP group and lipopolysaccharide (LPS) group. RAW264.7 cells were pre-treated with or without TLR4 inhibitor or MyD88 inhibitor. Quantitative RT-PCR and Western blot were performed to detect the mRNA and protein expressions, respectively...
January 14, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29325291/-hepatitis-b-core-antigen-promotes-invasion-of-hepatocellular-carcinoma-cell-line-hepg2-2-15-via-toll-like-receptor-4
#3
H R Hou, Y Kang, Y K Li, Y L Zeng, J F Wei, G G Ding, Z Peng, J Shang
Objective: To investigate the effect of hepatitis B core antigen (HBcAg) in promoting the invasion of hepatitis B virus (HBV)-related hepatocellular carcinoma cell line HepG2.2.15 and the role of Toll-like receptor 4 (TLR4) in the mechanism. Methods: TLR4 mRNA and protein expression in HepG2 cells and HepG2.2.15 cells was measured by reverse transcription real-time PCR and Western blot analysis, respectively. HepG2.2.15 cells were transfected with TLR4 specific small interfering RNA (siRNA) to silence TLR4 expression, and stimulated by recombinant HBcAg in culture...
December 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29321276/ifn-regulatory-factor-3-balances-th1-and-t-follicular-helper-immunity-during-nonlethal-blood-stage-plasmodium-infection
#4
Kylie R James, Megan S F Soon, Ismail Sebina, Daniel Fernandez-Ruiz, Gayle Davey, Urijah N Liligeto, Arya Sheela Nair, Lily G Fogg, Chelsea L Edwards, Shannon E Best, Lianne I M Lansink, Kate Schroder, Jane A C Wilson, Rebecca Austin, Andreas Suhrbier, Steven W Lane, Geoffrey R Hill, Christian R Engwerda, William R Heath, Ashraful Haque
Differentiation of CD4+ Th cells is critical for immunity to malaria. Several innate immune signaling pathways have been implicated in the detection of blood-stage Plasmodium parasites, yet their influence over Th cell immunity remains unclear. In this study, we used Plasmodium-reactive TCR transgenic CD4+ T cells, termed PbTII cells, during nonlethal P. chabaudi chabaudi AS and P. yoelii 17XNL infection in mice, to examine Th cell development in vivo. We found no role for caspase1/11, stimulator of IFN genes, or mitochondrial antiviral-signaling protein, and only modest roles for MyD88 and TRIF-dependent signaling in controlling PbTII cell expansion...
January 10, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29282308/b-cell-intrinsic-myd88-signaling-promotes-initial-cell-proliferation-and-differentiation-to-enhance-the-germinal-center-response-to-a-virus-like-particle
#5
Meijie Tian, Zhaolin Hua, Sheng Hong, Zhimin Zhang, Can Liu, Lin Lin, Jiaorong Chen, Wei Zhang, Xuyu Zhou, Fuping Zhang, Anthony L DeFranco, Baidong Hou
Although TLR signaling in B cells has been implicated in the germinal center (GC) responses during viral infections and autoimmune diseases, the underlying mechanism is unclear. Bacterial phage Qβ-derived virus-like particle (Qβ-VLP) contains TLR ligands, which can enhance Qβ-VLP-induced Ab response, including GC response, through TLR/MyD88 signaling in B cells. In this study, by examining Ag-specific B cell response to Qβ-VLP, we found that lack of B cell MyD88 from the beginning of the immune response led to a more severe defect in the GC scale than abolishing MyD88 at later time points of the immune response...
December 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29234326/toll-like-receptor-4-on-both-myeloid-cells-and-dendritic-cells-is-required-for-systemic-inflammation-and-organ-damage-after-hemorrhagic-shock-with-tissue-trauma-in-mice
#6
Kent Zettel, Sebastian Korff, Ruben Zamora, Adrian E Morelli, Sophie Darwiche, Patricia A Loughran, Greg Elson, Limin Shang, Susana Salgado-Pires, Melanie J Scott, Yoram Vodovotz, Timothy R Billiar
Trauma combined with hemorrhagic shock (HS/T) leads to systemic inflammation, which results in organ injury. Toll-like Receptor 4 (TLR4)-signaling activation contributes to the initiation of inflammatory pathways following HS/T but its cell-specific roles in this setting are not known. We assessed the importance of TLR4 on leukocytes of myeloid lineage and dendritic cells (DCs) to the early systemic inflammatory response following HS/T. Mice were subjected to HS/T and 20 inflammatory mediators were measured in plasma followed by Dynamic Bayesian Network (DBN) Analysis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29212908/naive-cd4-t-cells-carrying-a-tlr2-agonist-overcome-tgf-%C3%AE-mediated-tumor-immune-evasion
#7
Mohsen Ibrahim, Davide Scozzi, Kelsey A Toth, Donatella Ponti, Daniel Kreisel, Cecilia Menna, Elena De Falco, Antonio D'Andrilli, Erino A Rendina, Antonella Calogero, Alexander S Krupnick, Andrew E Gelman
TLR agonists are effective at treating superficial cancerous lesions, but their use internally for other types of tumors remains challenging because of toxicity. In this article, we report that murine and human naive CD4+ T cells that sequester Pam3Cys4 (CD4+ TPam3) become primed for Th1 differentiation. CD4+ TPam3 cells encoding the OVA-specific TCR OT2, when transferred into mice bearing established TGF-β-OVA-expressing thymomas, produce high amounts of IFN-γ and sensitize tumors to PD-1/programmed cell death ligand 1 blockade-induced rejection...
December 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29182620/broncho-vaxom-om-85-modulates-rhinovirus-docking-proteins-on-human-airway-epithelial-cells-via-erk1-2-mitogen-activated-protein-kinase-and-camp
#8
Michael Roth, Christian Pasquali, Daiana Stolz, Michael Tamm
BACKGROUND: Bronchial epithelial cells (BEC) are primary target for Rhinovirus infection through attaching to cell membrane proteins. OM-85, a bacterial extract, improves recovery of asthma and COPD patients after viral infections, but only part of the mechanism was addressed, by focusing on defined immune cells. OBJECTIVE: We therefore determined the effect of OM-85 on isolated primary human BEC of controls (n = 8), asthma patients (n = 10) and COPD patients (n = 9)...
2017: PloS One
https://www.readbyqxmd.com/read/29133782/mtor-intersects-antibody-inducing-signals-from-taci-in-marginal-zone-b-cells
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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