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MyD88 in T cells

Lorenza Tulli, Francesca Cattaneo, Juliette Vinot, Cosima T Baldari, Ugo D'Oro
Toll-like receptors (TLRs) play a key role in the activation of innate immune cells, in which their engagement leads to production of cytokines and co-stimulatory molecules. TLRs signaling requires recruitment of toll/IL-1R (TIR) domain-containing adaptors, such as MyD88 and/or TRIF, and leads to activation of several transcription factors, such as NF-κB, the AP1 complex, and various members of the interferon regulatory factor (IRF) family, which in turn results in triggering of several cellular functions associated with these receptors...
2018: Frontiers in Immunology
Allison M Weis, Raymond Soto, June L Round
The commensal microbiota influences many aspects of immune system regulation, including T cells, but molecular details of how this occurs are largely unknown. Here we review our findings that the microbiota regulates Erdr1, a secreted apoptotic factor, to control T cell survival. Erdr1 is highly upregulated in CD4+ T cells from germfree mice and antibiotic treated animals, and our study shows that Erdr1 is suppressed by the microbiota via Toll-like receptor signaling and MyD88 dependent pathways. Erdr1 functions in an autocrine fashion and promotes apoptosis through the FAS/FASL pathway...
March 15, 2018: Gut Microbes
Anne M R Schrader, Patty M Jansen, Rein Willemze, Maarten H Vermeer, Anne-Marie Cleton-Jansen, Sebastiaan F Somers, J H Hendrik Veelken, Ronald van Eijk, Willem Kraan, Marie José Kersten, Michiel van den Brand, Wendy B C Stevens, Daphne de Jong, Myrurgia Abdul Hamid, Bea C Tanis, Eduardus F M Posthuma, Marcel Nijland, Arjan Diepstra, Steven T Pals, Arjen H G Cleven, Joost S P Vermaat
No abstract text is available yet for this article.
March 7, 2018: Blood
Rajakumar Mandraju, Aakanksha Jain, Yajing Gao, Zhiming Ouyang, Michael V Norgard, Chandrashekhar Pasare
Activation of CD4 T cells by dendritic cells leads to their differentiation into various effector lineages. The nature of the effector lineage is determined by the innate cues provided by dendritic cells to newly primed T cells. Although the cytokines necessary for several effector lineages have been identified, the innate cues that drive Tfh lineage development remain unclear. Here we find that following priming, CD4 T cells undergoing clonal expansion acquire a transient Tfh-like phenotype before differentiating into other effector lineages...
March 5, 2018: Infection and Immunity
Matthew S Block, Robert A Vierkant, Peter F Rambau, Stacey J Winham, Philipp Wagner, Nadia Traficante, Aleksandra Tołoczko, Daniel G Tiezzi, Florin Andrei Taran, Peter Sinn, Weiva Sieh, Raghwa Sharma, Joseph H Rothstein, Teresa Ramón Y Cajal, Luis Paz-Ares, Oleg Oszurek, Sandra Orsulic, Roberta B Ness, Gregg Nelson, Francesmary Modugno, Janusz Menkiszak, Valerie McGuire, Bryan M McCauley, Marie Mack, Jan Lubiński, Teri A Longacre, Zheng Li, Jenny Lester, Catherine J Kennedy, Kimberly R Kalli, Audrey Y Jung, Sharon E Johnatty, Mercedes Jimenez-Linan, Allan Jensen, Maria P Intermaggio, Jillian Hung, Esther Herpel, Brenda Y Hernandez, Andreas D Hartkopf, Paul R Harnett, Prafull Ghatage, José M García-Bueno, Bo Gao, Sian Fereday, Ursula Eilber, Robert P Edwards, Christiani B de Sousa, Jurandyr M de Andrade, Anita Chudecka-Głaz, Georgia Chenevix-Trench, Alicia Cazorla, Sara Y Brucker, Jennifer Alsop, Alice S Whittemore, Helen Steed, Annette Staebler, Kirsten B Moysich, Usha Menon, Jennifer M Koziak, Stefan Kommoss, Susanne K Kjaer, Linda E Kelemen, Beth Y Karlan, David G Huntsman, Estrid Høgdall, Jacek Gronwald, Marc T Goodman, Blake Gilks, María José García, Peter A Fasching, Anna de Fazio, Suha Deen, Jenny Chang-Claude, Francisco J Candido Dos Reis, Ian G Campbell, James D Brenton, David D Bowtell, Javier Benítez, Paul D P Pharoah, Martin Köbel, Susan J Ramus, Ellen L Goode
OBJECTIVE: To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival. PATIENTS AND METHODS: We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time...
March 2018: Mayo Clinic Proceedings
Guomu Liu, Xiaoyu Zhai, Hongyue Zhou, Xiaoyu Yang, Nannan Zhang, Guixiang Tai, Weihua Ni
Our previous study demonstrated that maltose-binding protein (MBP) activated Th1 through the TLR2-mediated MyD88-dependent pathway and the TLR4-mediated TRIF-dependent pathway. The combination of MBP and BCG synergistically induced Th1 activation, and the TLR2/9-mediated MyD88-dependent pathway is involved in this process. To further explore this mechanism, we stimulated purified mouse CD4 + T cells with MBP and BCG in vitro. The results demonstrated that MBP combined with BCG synergistically increased IFN-γ production and TLR2/4/9 expression, suggesting the involvement of TLR2/4/9 in the combination-induced Th1 activation...
February 12, 2018: Cellular Immunology
Xingli Zhao, Zhuoran Zhang, Dayson Moreira, Yu-Lin Su, Haejung Won, Tomasz Adamus, Zhenyuan Dong, Yong Liang, Hongwei H Yin, Piotr Swiderski, Raju K Pillai, Larry Kwak, Stephen Forman, Marcin Kortylewski
Growing evidence links the aggressiveness of non-Hodgkin's lymphoma, especially the activated B cell-like type diffuse large B cell lymphomas (ABC-DLBCLs) to Toll-like receptor 9 (TLR9)/MyD88 and STAT3 transcription factor signaling. Here, we describe a dual-function molecule consisting of a clinically relevant TLR9 agonist (CpG7909) and a STAT3 inhibitor in the form of a high-affinity decoy oligodeoxynucleotide (dODN). The CpG-STAT3dODN blocked STAT3 DNA binding and activity, thus reducing expression of downstream target genes, such as MYC and BCL2L1, in human and mouse lymphoma cells...
January 17, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
T Zhang, J Wu, N Ungvijanpunya, O Jackson-Weaver, Y Gou, J Feng, T V Ho, Y Shen, J Liu, S Richard, J Jin, G Hajishengallis, Y Chai, J Xu
The balance between pro- and anti-inflammatory signals maintains tissue homeostasis and defines the outcome of chronic inflammatory diseases such as periodontitis, a condition that afflicts the tooth-supporting tissues and exerts an impact on systemic health. The induction of tissue inflammation relies heavily on Toll-like receptor (TLR) signaling, which drives a proinflammatory pathway through recruiting myeloid differentiation primary response gene 88 (MyD88) and activating nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB)...
February 1, 2018: Journal of Dental Research
Qin Wang, Julie Delcorde, Tracy Tang, Gregory P Downey, Christopher A McCulloch
IL-1 signaling is adhesion-restricted in many cell types, but the mechanism that drives it is not defined. We screened for proteins recruited to nascent adhesions in IL-1-treated human fibroblasts with tandem mass tag-mass spectrometry. We used fibronectin bead preparations to enrich 10 actin-associated proteins. There was a 1.2 times log 2-fold enrichment of actin capping protein (ACP) at 30 min after IL-1 stimulation. Knockdown (KD) of ACP by siRNA reduced IL-1-induced ERK activation(by 56%, matrix metalloproteinase-3 (MMP-3) expression by 48%, and MMP-9 expression by 62% (in all reductions, P < 0...
January 22, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Carly A Dillen, Bret L Pinsker, Alina I Marusina, Alexander A Merleev, Orly N Farber, Haiyun Liu, Nathan K Archer, Da B Lee, Yu Wang, Roger V Ortines, Steven K Lee, Mark C Marchitto, Shuting S Cai, Alyssa G Ashbaugh, Larissa S May, Steven M Holland, Alexandra F Freeman, Loren G Miller, Michael R Yeaman, Scott I Simon, Joshua D Milner, Emanual Maverakis, Lloyd S Miller
The mechanisms that mediate durable protection against Staphylococcus aureus skin reinfections are unclear, as recurrences are common despite high antibody titers and memory T cells. Here, we developed a mouse model of S. aureus skin reinfection to investigate protective memory responses. In contrast with WT mice, IL-1β-deficient mice exhibited poor neutrophil recruitment and bacterial clearance during primary infection that was rescued during secondary S. aureus challenge. The γδ T cells from skin-draining LNs utilized compensatory T cell-intrinsic TLR2/MyD88 signaling to mediate rescue by trafficking and producing TNF and IFN-γ, which restored neutrophil recruitment and promoted bacterial clearance...
February 5, 2018: Journal of Clinical Investigation
T Suzuki, J Sakabe, K Kamiya, A Funakoshi, Y Tokura
BACKGROUND: Plasmacytoid dendritic cells (pDCs) are involved in the pathogenesis of psoriasis by secreting interferon-α. Vitamin D3 analogues are widely used to treat psoriasis, and the representative analogue calcipotriol (CAL) uniquely downregulates the cytokine production and chemotactic activity of pDCs. However, the molecular mechanism of action of CAL is not well understood. AIM: To investigate effects of CAL on the Toll-like receptor 9-myeloid differentiation primary response gene 88 (TLR9-MyD88) signalling pathway, which induces cytokine production, in murine pDCs...
February 1, 2018: Clinical and Experimental Dermatology
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
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
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
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
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
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
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 Pam3 Cys4 (CD4+ TPam3 ) become primed for Th 1 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...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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
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
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