Podcasts about tlr3

TWiV reviews universal vaccine initiative at NIAID, shut down of the Integrated Research Facility at Ft. Detrick, modeling the reemergence of infectious diseases as vaccination rates drop, and bacterial outer membrane vesicles bound to bacteriophages modulate neutrophil responses to bacterial infection. Hosts: Vincent Racaniello, Alan Dove, and Jolene Ramsey Subscribe (free): Apple Podcasts, RSS, email Become a patron of TWiV! Links for this episode Support science education at MicrobeTV ASV 2025 Paul has Measles (YouTube, virology blog) Universal vaccine project (NIAID, CIDRAP) Measles update (US, Texas) Integrated Research Lab closed (Telegraph) Modeling reemergence of infectious diseases (JAMA) Outer membrane vesicles attached to phage (Front Cell Inf Micro) Pf phage review (Front Immunol) Letters read on TWiV 1215 Timestamps by Jolene Ramsey. Thanks! Weekly Picks Alan – A Paradise Built in Hell, by Rebecca Solnit (and here's my review of it) Jolene – Virology course student communication projects, Spring 2025 Vincent – Vaccine Education Center Intro music is by Ronald Jenkees Send your virology questions and comments to twiv@microbe.tv Content in this podcast should not be construed as medical advice.

GDP Script/ Top Stories for May 31st Publish Date:  May 31st              From the Ingles Studio Welcome to the Gwinnett Daily Post Podcast. Today is Friday, May 31st and Happy 94th Birthday to actor Clint Eastwood.   I'm Bruce Jenkins and here are your top stories presented by Gwinnett KIA Mall of Georgia. Gwinnett Police Helicopter Helps Locate Missing Child Computer Glitch Sends Tax Appeal Hearings Email to Many Gwinnettians Marine From Buford Carries Honor and Remember Flag at Virginia Run for The Fallen Memorial Run All of this and more is coming up on the Gwinnett Daily Post podcast, and if you are looking for community news, we encourage you to listen daily and subscribe! Break 1: MOG   STORY 1: Gwinnett Police Helicopter Helps Locate Missing Child Gwinnett County Police found a critically missing 15-year-old girl on Wednesday using a police helicopter. The girl's mother reported her missing around 11:40 a.m. after an argument, discovering she had left their Lawrenceville home without shoes. Due to a medical condition requiring supervision, the Gwinnett Police Aviation Unit was called in. The helicopter quickly located the girl, and officers on the ground, guided by Corporal Hanna, found her upset but safe on a sidewalk. Hanna calmed the girl and safely returned her home. The case showcased the police department's coordinated efforts and crisis training. STORY 2: ERROR: Computer Glitch Sends Tax Appeal Hearings Email to Many Gwinnettians On Memorial Day, many Gwinnett County homeowners received erroneous emails about participating in Board of Equalization appeal hearings due to a computer glitch. The emails, sent between 10:42 and 11:43 a.m., were caused by a coding error and affected "several thousand" homeowners. The emails, which included WebEx links for hearings, caused confusion and concerns about potential scams. Arefeen Chowdhury, a candidate for Gwinnett tax commissioner, demanded answers. The county sent a follow-up email explaining the mistake and has taken steps to correct the issue and prevent future occurrences. STORY 3: Marine From Buford Carries Honor And Remember Flag at Virginia Run For The Fallen Memorial Run On May 4, U.S. Marines with the Security Battalion participated in the 12th Annual Virginia Run for the Fallen at Marine Corps Base Quantico, running with the American and Honor and Remember flags. The event, involving Gold Star families and veterans, is part of a four-day, 250-mile tribute to honor Virginia service members who died during the War on Terror. Lance Cpl. Jacob Shelton and Cpl. Jose Crosby carried the flags for this segment, joined by Cpl. Marina Camponescki and Cpl. Jorge Ruiz. Eight Marines volunteered to honor 18 fallen service members from all U.S. Armed Forces branches. We have opportunities for sponsors to get great engagement on these shows. Call 770.874.3200 for more info. We'll be right back.   Break 2: TOM WAGES   STORY 4: Biden administration, Georgia officials applaud debut of Plant Vogtle expansion On May 29, Georgia Power announced that the Unit 3 nuclear reactor at Plant Vogtle is fully operational. U.S. Energy Secretary Jennifer Granholm and National Climate Advisor Ali Zaidi will celebrate this milestone, highlighting Plant Vogtle as the largest U.S. nuclear power plant and a major source of carbon-free electricity. The expansion, completed after 15 years and $36.8 billion, is expected to power one million homes and create high-quality jobs. However, a report by Georgia consumer groups criticizes the project for severe cost overruns and delays, estimating significant future rate hikes for Georgia Power customers. STORY 5: New study suggests statins may help prevent cancer A new study suggests that statins, commonly used to lower cholesterol, may also prevent cancer by blocking a key inflammatory protein. Published in Nature Communications, the research shows that statins can obstruct the TLR3/4 and TBK1-IRF3 pathways, which are involved in cancer development from chronic inflammation. Led by Professor Shawn Demehri of Massachusetts General Hospital, the study found that the statin pitavastatin effectively suppresses the IL-33 protein, reducing inflammation and preventing cancer in mice. Analysis of health records from over 200 million people indicated that pitavastatin use is linked to a significantly lower risk of chronic pancreatitis and pancreatic cancer. The findings suggest that statins may offer a safe and effective means to combat inflammation-related cancers.   We'll be back in a moment.   Break 3: INGLES 7   STORY 6: Atlanta Women's Chorus to Perform Saturday at Lawrenceville Arts Center The Atlanta Women's Chorus will present "Phoenix Rising," a multimedia performance commemorating American history with a hopeful message of inclusiveness, this Saturday at the Lawrenceville Arts Center. The two-hour show, directed by Melissa Arasi, explores themes from the Civil War to gay rights and Black Lives Matter, aiming to unite and inspire without judgment. Celebrating its 10th anniversary, the chorus partners with Women Engaged, a nonprofit promoting women's rights and civic engagement. The performance includes choral music, actors, speakers, and video segments. For more information and tickets, visit www.voicesofnote.org. STORY 7: Abril Olivas tapped to serve as Barrow County Clerk Abril Olivas has been appointed as the new clerk for Barrow County Government, starting June 3. She will manage official county records and provide executive support to the Board of Commissioners and the County Manager. Currently the Deputy Clerk for Hall County, Olivas brings extensive experience in administrative and local government roles. Barrow County Manager Srikanth Yamala praised her skills and energy. Olivas, a member of the Georgia Clerks Association, has also worked as a legal assistant for 11 years. She expressed enthusiasm about her new role and commitment to serving Barrow County.   We'll have final thoughts after this.   Break 4: INGLES 8   Signoff – Thanks again for hanging out with us on today's Gwinnett Daily Post Podcast. If you enjoy these shows, we encourage you to check out our other offerings, like the Cherokee Tribune Ledger Podcast, the Marietta Daily Journal, or the Community Podcast for Rockdale Newton and Morgan Counties. Read more about all our stories and get other great content at gwinnettdailypost.com Did you know over 50% of Americans listen to podcasts weekly? Giving you important news about our community and telling great stories are what we do. Make sure you join us for our next episode and be sure to share this podcast on social media with your friends and family. Add us to your Alexa Flash Briefing or your Google Home Briefing and be sure to like, follow, and subscribe wherever you get your podcasts. Produced by the BG Podcast Network   Show Sponsors: www.ingles-markets.com  www.wagesfuneralhome.com www.kiamallofga.com   #NewsPodcast #CurrentEvents #TopHeadlines #BreakingNews #PodcastDiscussion #PodcastNews #InDepthAnalysis #NewsAnalysis #PodcastTrending #WorldNews #LocalNews #GlobalNews #PodcastInsights #NewsBrief #PodcastUpdate #NewsRoundup #WeeklyNews #DailyNews #PodcastInterviews #HotTopics #PodcastOpinions #InvestigativeJournalism #BehindTheHeadlines #PodcastMedia #NewsStories #PodcastReports #JournalismMatters #PodcastPerspectives #NewsCommentary #PodcastListeners #NewsPodcastCommunity #NewsSource #PodcastCuration #WorldAffairs #PodcastUpdates #AudioNews #PodcastJournalism #EmergingStories #NewsFlash #PodcastConversationsSee omnystudio.com/listener for privacy information.

In this study, researchers found that the genetic material from the virus and possibly other parts activate TLR3 receptors. These in turn cause the cells to release IFN1. IFN1 works on the intestinal cells via STAT1 pathway to down-regulate ACE2 receptors and B0AT1 channels. The result is reduced absorption of tryptophan leading to reduced serotonin production in the body. They also found that IFN1 activates platelets leading to micro thrombi and further reduction of serotonin as platelets are a huge reservoir of serotonin. Researchers also found that MAO activity was increased. Vagal activity was reduced leading to the hippocampal reduction in function as well. The researchers suggest using tryptophan precursor supplement (5HTP - 5 hydroxytryptophan) and SSRI medications to rescue serotonin levels in long COVID patients. DrBeen: Medical Education Onlinehttps://www.drbeen.com/ FLCCC | Front Line COVID-19 Critical Care Alliancehttps://covid19criticalcare.com/ URL List (Nov. 24 2023) Serotonin reduction in post-acute sequelae of viral infection: Cellhttps://www.cell.com/cell/fulltext/S0092-8674(23)01034-6#gr2 Serotonin in Platelets - ScienceDirecthttps://www.sciencedirect.com/science/article/abs/pii/B978012800050200005X IJMS | Free Full-Text | The Mechanism of Secretion and Metabolism of Gut-Derived 5-Hydroxytryptaminehttps://www.mdpi.com/1422-0067/22/15/7931 ijms-22-07931-g001.png (3550×2309)https://www.mdpi.com/ijms/ijms-22-07931/article_deploy/html/images/ijms-22-07931-g001.png Uptake and release of serotonin by blood platelets. Serotonin is taken... | Download Scientific Diagramhttps://www.researchgate.net/figure/Uptake-and-release-of-serotonin-by-blood-platelets-Serotonin-is-taken-up-from-the_fig2_367097021 Indoleamine 2,3-dioxygenase - Wikipediahttps://en.wikipedia.org/wiki/Indoleamine_2,3-dioxygenase#:~:text=Indoleamine%2Dpyrrole%202%2C3%2D,female%20genital%20tract%20or%20placenta. Frontiers | Kynurenine Pathway Metabolites as Biomarkers for Amyotrophic Lateral Sclerosishttps://www.frontiersin.org/articles/10.3389/fnins.2019.01013/full Toll-like receptor 3 (TLR3) regulation mechanisms and roles in antiviral innate immune responses - PMChttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377577/#:~:text=Toll%2Dlike%20receptor%203%20(TLR3)%20is%20a%20member%20of,establishing%20an%20antiviral%20host%20response. Mechanisms of type-I- and type-II-interferon-mediated signalling | Nature Reviews Immunologyhttps://www.nature.com/articles/nri1604 Disclaimer:This video is not intended to provide assessment, diagnosis, treatment, or medical advice; it also does not constitute provision of healthcare services. The content provided in this video is for informational and educational purposes only. Please consult with a physician or healthcare professional regarding any medical or mental health related diagnosis or treatment. No information in this video should ever be considered as a substitute for advice from a healthcare professional.

A new research paper was published in Oncotarget on August 3, 2022, entitled, “A novel mechanism of regulation of the oncogenic transcription factor GLI3 by toll-like receptor signaling.” The transcription factor GLI3 is a member of the GLI family and has been shown to be regulated by canonical hedgehog (HH) signaling through smoothened (SMO). Little is known about SMO-independent regulation of GLI3. “Hedgehog (HH) signaling is well known for its role in embryonic development, cancer and inflammation [1–4]. At the center of HH signaling are the 2 receptors patched (PTCH1) and smoothened (SMO) along with GLI transcription factors [5]. In the absence of HH ligand, PTCH1 inhibits SMO.” In this study, researchers (Stephan J. Matissek, Mona Karbalivand, Weiguo Han, Ava Boutilier, Estefania Yzar-Garcia, Laura L. Kehoe, Devin Storm Gardner, Adam Hage, Krista Fleck, Vicki Jeffers, Ricardo Rajsbaum, and Sherine F. Elsawa) from the University of New Hampshire and University of Texas Medical Branch identified toll-like receptor (TLR) signaling as a novel pathway regulating GLI3 expression. The researchers showed that GLI3 expression is induced by LPS/TLR4 in human monocyte cell lines and peripheral blood CD14+ cells. Further analysis identified TRIF, but not MyD88, signaling as the adapter used by TLR4 to regulate GLI3. Using pharmacological and genetic tools, they identified IRF3 as the transcription factor regulating GLI3 downstream of TRIF. “Furthermore, using additional TLR ligands that signal through TRIF such as the TLR4 ligand, MPLA and the TLR3 ligand, Poly(I:C), we confirm the role of TRIF-IRF3 in the regulation of GLI3.” They found that IRF3 directly binds to the GLI3 promoter region and this binding was increased upon stimulation of TRIF-IRF3 with Poly(I:C). Using Irf3−/− MEFs, the researchers found that Poly(I:C) stimulation no longer induced GLI3 expression. Finally, using macrophages from mice lacking Gli3 expression in myeloid cells (M-Gli3−/−), they found that in the absence of Gli3, LPS stimulated macrophages secrete less CCL2 and TNF-α compared with macrophages from wild-type (WT) mice. “Taken together, these results identify a novel TLR-TRIF-IRF3 pathway that regulates the expression of GLI3 that regulates inflammatory cytokines and expands our understanding of the non-canonical signaling pathways involved in the regulation of GLI transcription factors.” DOI: https://doi.org/10.18632/oncotarget.28261 Correspondence to: Sherine F. Elsawa – Email: sherine.elsawa@unh.edu Keywords: GLI3, inflammation, TLR About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com. Oncotarget Journal Office 6666 East Quaker Str., Suite 1A Orchard Park, NY 14127 Phone: 1-800-922-0957 (option 2)

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.11.377713v1?rss=1 Authors: Choudhury, A., Das, N. C., Patra, R., Bhattacharya, M., Mukherjee, S. Abstract: The worldwide outbreak of COVID-19 pandemic caused by SARS-CoV-2 leads to loss of mankind and global economic stability. The continuous spreading of the disease and its pathogenesis takes millions of lives of peoples and the unavailability of appropriate therapeutic strategy makes it much more severe. Toll-like receptors (TLRs) are the crucial mediators and regulators of host immunity. The role of several TLRs in immunomodulation of host by SARS-CoV-2 is recently demonstrated. However, the functionality of human intracellular TLRs including TLR3,7,8 and 9 is still being untested for sensing of viral RNA. This study is hoped to rationalize the comparative binding and sensing of SARS-CoV-2 mRNA towards the intracellular TLRs, considering the solvent-based force-fields operational in the cytosolic aqueous microenvironment that predominantly drive these reactions. Our in-silico study on the binding of all mRNAs with the intracellular TLRs shown that the mRNA of NSP10, S2, and E proteins of SARS-CoV-2 are potent enough to bind with TLR3, TLR9, and TLR7 and trigger downstream cascade reactions, and may be used as an option for validation of therapeutic option and immunomodulation against COVID-19. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.09.333815v1?rss=1 Authors: Nichols, E. K., Chuang, H.-C., Davis, M. T., Geiger, K. M., Li, R. Z., Arnold, M. L., Lin, P. M., Misra, R., Coscoy, L., Saijo, K. Abstract: Maternal immune activation (MIA) increases likelihood of altered neurodevelopmental outcomes. Maternal cytokines are proposed to affect fetal brain development in mice; however, the contribution of fetal immunity to neurodevelopmental disorders is largely unexplored. Here, we show that MIA mediated by Toll-like receptor 3 (TLR3), but not other TLRs, induces a specific set of behavioral phenotypes including decreased sociability and increased restricted repetitive behavior in offspring. Accordingly, these behavioral phenotypes were absent when offspring were deficient for Trif, the downstream adapter molecule of TLR3. Using single-cell RNA sequencing, we identified clusters of border-associated macrophages that were significantly enriched in the fetal brain following TLR3-MIA, and these clusters were diminished in Trif-/- fetal brains. Moreover, we found that triggering TLR3-TRIF in offspring can occur through transplacental viral infection, resulting in altered behavioral phenotypes. Collectively, our data indicate that fetal innate immunity contributes to MIA-induced atypical behaviors in mice. Copy rights belong to original authors. Visit the link for more info

Monday Locker Room w/Michael Jargo & Ric Vickrey... March 2, 2020.   The Outbreak is Sweeping the Globe and if the Coronavirus Doesn't Have to Terrified than WWE Creative will Certainly Get You There. On this Week's Episode of the Monday Locker Room, #DemHTMBoys Jargo & RBV are Talking All the Big News that News from Around the World of Pro Wrestling.    On the Run... Coronavirus Infects the World of Pro Wrestling. Revolution and What's Next for AEW. Ring of Honor Happenings. WWE Creative Not Even Pretending to Care. Did You Realize Elimination Chamber is a Week Away? A Loaded RAW Preview.   Social Media Links: On Twitter: @notjargo @therealrbv @htmpwpod @haminmediagroup Facebook.com/haminmediagroup Facebook.com/hittingthemarks Instagram: htmpwpod hittingthemarks.com hackerhamin.podbean.com

The TWiM team presents an extracellular bacterium associated with Paramecium, and induction of antiviral immunity by a bacteriophage that prevents bacterial clearance. Subscribe to TWiM (free) on iTunes, Google Podcasts, Stitcher, Android, RSS, or by email. You can also listen on your mobile device with the Microbeworld app. Become a Patron of TWiM! Bacteria on the outside of paramecia (ISME) Phage trigger antiviral immunity (Science) Image credit Letters read on TWiM 198 Music used on TWiM is composed and performed by Ronald Jenkees and used with permission. Send your microbiology questions and comments to twim@microbe.tv

The TWiM team notes the passing of Allan Campbell, and explains how aminoglycoside antibiotics like neomycin enhance host resistance to viral infection. Hosts:  Vincent Racaniello, Michael Schmidt, and Michele Swanson. Subscribe to TWiM (free) on iPhone, Android, RSS, or by email. You can also listen on your mobile device with the Microbeworld app. Become a patron of TWiM. Links for this episode: Happy Birthday, Elio! (STC) Allan Campbell, 88 (Stanford News) Life in Science by Allan Campbell (Bacteriophage) Aminoglycosides inhibit viral infection (Nat Micro) Image credit Letters read on TWiM 175 Send your microbiology questions and comments (email or recorded audio) to twim@microbe.tv

Carlos Gorbea discusses how a subset of proteasomes attenuates TLR3-mediated antiviral signaling.

Hosts: Vincent Racaniello, Alan Dove, Dickson Despommier, and Kathy Spindler Vincent, Alan, Dickson, and Kathy discuss how the innate immune response to viral infection influences the production of pluripotent stem cells, and the diverse mobilome of giant viruses. Links for this episode: Innate immunity and nuclear reprogramming (Cell) Viruses affect cell reprogramming (The Scientist) Cell-penetrating peptides (Trends Mol Med) Provirophages and transpovirons (PNAS) Organic Lake photo and map Letters read on TWiV 206 Weekly Science Picks Alan - Locust by Jeffery A. LockwoodDickson - Nikon Small World Contest 2012Kathy - Influenza EncyclopediaVincent - Dengue fever sweeps India (NY Times) Listener Pick of the Week Allison - Fred Guterl on The Daily Show Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv.

Conventional cancer therapies like surgery, radiation and chemotherapy help to eliminate primary tumor masses but often fail to eradicate disseminated tumor cells. However, it is such residual tumor cells that frequently underlie metastasis and relapse. Major obstacles for targeting such cells are wide spread dissemination and long-term persistence in niches that are difficult to reach. For example, many patients with acute myeloid leukemia (AML) show persistence of leukemia after chemotherapy – so-called minimal residual disease (MRD) – which confers a life-threatening risk for relapse in over 70% of patients. Arming the immune system to attack residual tumor cells has high therapeutic potential since immune cells can patrol the body to find and destroy residual tumor cells. Therapeutic approaches using the immune system - so-called immunotherapies - can take several forms. My project concentrated on preclinical studies of two strategies: 1) use of dendritic cells (DC) for therapeutic vaccination and 2) adoptive T cell therapy with lymphocytes expressing transgenic T cell receptors (TCR) specific for tumor-associated antigens (TAA). In therapeutic vaccination a highly potent vaccine is needed to induce a valid immune response in patients with cancer. Effective antitumor immunity requires mobilization of IFN-γ-producing CD4+ T cells (Th1 cells) and lymphocytes with cytotoxic function, including cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. In my studies, high potency vaccines were developed using mature DC generated in 3 days (3d-mDC) that were stimulated with synthetic Toll-like receptor TLR3 and/or TLR7/8 agonists. This TLR stimulation mimics DC interaction with viruses and causes mDC to secrete the bioactive form of IL-12, supporting induction of effector cells. Characterization in vitro showed that TLR-activated 3d-mDC were superior to conventional 7d-mDC in capacity to induce Th1 cells as well as CTL. A humanized mouse model was established to verify these observations in vivo. NOD/scid IL2Rgnull mice, lacking murine T, B and NK cells, were reconstituted with human peripheral mononuclear cells and vaccinated with 3d-mDC, stimulated or not with TLR agonists, and conventional 7d-mDC. Induction of CTL was quantified ex vivo using splenocyte populations containing human lymphocytes. The in vivo results were concordant with in vitro observations, demonstrating the superior capacity of 3d-mDC that were stimulated with TLR agonists to induce CTL. Adoptive T cell therapy using TCR-modified lymphocytes represents a second powerful way to provide patients with specific antitumor immunity. Here previously isolated TCR gene sequences are introduced into activated patient-derived lymphocytes, assigning them new antigen specificities. First, T cells must be isolated with TAA specificities that express high-affinity TCR which effectively recognize tumor cells. It was contended that T cell stimulation using peptide-epitopes from TAA presented on foreign MHC would allow isolation of high-affinity TCR, since these T cells had not yet undergone negative selection in the thymus. This contention was proved in individual experiments, as described in this thesis, for the antigens tyrosinase, survivin and HMMR (hyaluronan-mediated motility receptor). Since survivin and HMMR are broadly expressed in AML, TCR specific for these TAA were isolated and subsequently transferred into recipient lymphocytes. Expression of survivin-specific TCR resulted in MHC-restricted death of transduced lymphocytes due to their elevated survivin expression after activation. This precludes use of survivin-specific TCR for therapy of AML. In contrast, transfer of an HMMR-specific TCR yielded effector lymphocytes that effectively killed AML cells in vitro. The behavior in vivo of TCR transduced lymphocytes is crucial for therapeutic outcome. To explore this capacity a xenograft mouse model was established using solid and disseminated human tumor cells injected into NOD/scid IL2Rgnull mice. Adoptive transfer of lymphocytes expressing an HMMR-specific TCR into tumor-bearing mice resulted in significant retardation of tumor outgrowth. Adoptive transfer of memory-like lymphocytes with higher proliferative potential and prolonged in vivo survival may also affect tumor growth. Analyses in vivo and in vitro showed that IL-15-induced effector memory T cells conferred the most potent antitumor immunity. In summary, this work provides evidence for potent in vivo antitumor effects by either using DC-based vaccines or adoptive transfer of TCR transduced lymphocytes, opening application of both strategies for immunotherapy of cancer.

Background: Active dendritic cell (DC) immunization protocols are rapidly gaining interest as therapeutic options in patients with acute myeloid leukemia (AML). Here we present for the first time a GMP-compliant 3-day protocol for generation of monocyte-derived DCs using different synthetic Toll-like receptor (TLR) agonists in intensively pretreated patients with AML. Methods: Four different maturation cocktails were compared for their impact on cell recovery, phenotype, cytokine secretion, migration, and lymphocyte activation in 20 AML patients and 25 healthy controls. Results: Maturation cocktails containing the TLR7/8 agonists R848 or CL075, with and without the addition of the TLR3 agonist poly(I:C), induced DCs that had a positive costimulatory profile, secreted high levels of IL-12(p70), showed chemotaxis to CCR7 ligands, had the ability to activate NK cells, and efficiently stimulated antigen-specific CD8(+) T cells. Conclusions: Our results demonstrate that this approach translates into biologically improved DCs, not only in healthy controls but also in AML patients. This data supports the clinical application of TLR-matured DCs in patients with AML for activation of innate and adaptive immune responses.

Thu, 20 May 2010 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/11548/ https://edoc.ub.uni-muenchen.de/11548/1/Beeck_Stefan.pdf Beeck, Stefan

In episode 27 of This Week in Virology, hosts Vincent Racaniello, Alan Dove, Dick Despommier, and Saul Silverstein revisit an ebola virus needlestick accident, and discuss the role of TLR3 in formation of Negri bodies, a New England college closed by norovirus gastroenteritis, hand, foot, and mouth disease outbreak in China, and the exit of herpes simplex virus from latency by synthesis of VP16. Links for this episode: Update on ebolavirus needlestick accident Formation of Negri bodies depend upon TLR3 Norovirus outbreak closes New England college Hand, foot, and mouth disease outbreak in China Synthesis of VP16 coordinates herpes simplex virus exit from latency Science blog of the week: Biocurious Science podcast pick of the week: NPR’s Science Friday Science book of the week: A Conspiracy of Cells by Michael Gold Dick’s pick: Andros Island Bonefish Club Saul’s pick: Secret Science Club

Background/Aims: Viral infections are a major problem worldwide and many of them are complicated by virally induced glomerulonephritides. Progression of kidney disease to renal failure is mainly attributed to the development of renal fibrosis characterized by the accumulation of extracellular matrix components in the mesangial cell compartment and the glomerular basement membrane. Plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (t-PA) are major regulators of plasmin generation and play an important role in generation and degradation of glomerular extracellular matrix components. Viral receptors expressed by mesangial cells (MC) are known to be key mediators in immune-mediated glomerulonephritis. We investigated the effect of stimulation of the viral receptors toll-like receptor 3 (TLR3) and retinoic acid-inducible gene I (RIG-I) on the expression of PAI-1 and t-PA. Methods: Expression of PAI-1 and t-PA in immortalized human MC stimulated with polyriboinosinic: polyribocytidylic acid {[}poly(I:C)] RNA and cytokines were analyzed by real-time RT-PCR and ELISA. Results: Incubation of MC with poly(I:C) RNA to activate the viral receptors TLR3 and RIG-I upregulates the expression of PAI-1 and t-PA. Knockdown of viral receptors with specific siRNA abolishes the induction of PAI-1 and t-PA. Conclusion: For the first time a link between the activation of viral receptors on MC and potentially causative agents in the development of glomerulosclerosis and tubulointerstitial fibrosis is shown. The progression of inflammatory processes to glomerulosclerosis can be postulated to be directly enhanced by viral infection. Copyright (C) 2009 S. Karger AG, Basel

Olá, Viva. Décima edição do podcast "Journal Club Imunoterapia tumoral". Apresento-vos o artigo Dendritic cell preactivation impairs MHC class II presentation of vaccines and endogenous viral antigens Young et al 2007 PNAS 104: 17753 Este artigo demonstra que células dendriticas no seu estado maturo in vivo são incapazes de induzir respostas imunológicas específicas de um antigénio, e sobretudo que a razão que justifica este comportamento é a ausência de sintese das moléculas alpha e beta do heterodimero MHC classe II após maturação. Os autores observam que mesmo após maturação, as células continuam a apresentar capacidade de endocitose e capacidade de degradar antigénios solúveis e antigénios endogenos à célula dendritica, tais como antigénios virais. As células dendriticas são células fundamentais no desenvolvimento de respostas imunológicas in vivo sobretudo pela sua capacidade de induzirem a activação de linfócitos T naive. Para induzir a maturação das células dendriticas in vivo, os autores injectam CpG 1668 em ratinhos, o que gera uma maturação generalizada das células dendriticas encontradas no baço destes ratinhos. Semelhante fenómeno pode ser encontrado em condições de choque séptico ou em situações de infecções parasiticas como por exemplo a malária. O CpG são moléculas de ADN lineares ricas em sequências de nucleotideos citosina e guanina e que tem a propriedade de induzir fortes respostas imunológicas. Tal acontece porque existem nas células do sistema imunológico receptores que se ligam a este tipo de moléculas muito comuns em agentes infecciosos: os receptores Toll-like.  Estes receptores Toll-like são vários e reconhecem cada um deles um tipo específico de moléculas, eg TLR9 reconhece CpG, TLR4 reconhece LPS, TLR3 reconhece Poly I:C. Para mais informações deem uma olhada no link seguinte do wikipedia. Embora in vitro existam vários estudos sobre os aspectos funcionais das células dendriticas, estudos in vivo são raros. Este estudo é por isso valioso para reforçar o nosso conhecimento dos processos imunológicos. Um abraço e até breve. Pedro

Nucleic acids that occur free or as immune complexes may trigger immune activation leading to aggravation of diseases with autoimmune predisposition. TLR3 and TLR 9 represent receptors that signal for viral and bacterial nucleic acids respectively. pI:C RNA, a synthetic double stranded RNA with identical properties to that viral origin activates TLR3 led to aggravation of lupus nephritis, a form of immune complex glomerulonephritis, in pre-existing lupus in MRLlpr/lpr mice. Exposure to pI:C RNA (a structural analogue of viral dsRNA) can aggravate lupus nephritis through TLR3 on antigen-presenting cells and glomerular mesangial cells. pI:C RNA–induced cytokine and chemokine production represents a major mechanism in this context. Likewise, CpG DNA a classical activator for TLR-9 led to disease aggravation in this mouse model albeit, through mechanisms that shared some commonality as well as differences to that observed with pI:C RNA. Apparently, pathogen associated immunomodulation relates to the cell-type-specific expression pattern of the respective pattern-recognition receptor. dsRNA-induced disease activity is independent of B cell activation and humoral antichromatin immunity in experimental SLE and therefore differs from CpG-DNA–induced autoimmunity. These findings contribute to the understanding of pathogen-associated modulation of autoimmunity but may also be involved in the pathogenesis of other types of inflammatory kidney diseases, e.g., flares of IgA nephropathy, renal manifestations of chronic hepatitis C virus infection, and renal vasculitis. Further, besides signifying the role of foreign and self-DNA as a pathogenic factor in autoimmune disease activity in lupus, this detailed study reveals, that certain synthetic G-rich nucleic acids may potentially block nucleic acid specific TLR functions and thus prove beneficial in arresting disease activity during progressive systemic lupus. One such G-rich DNA employed in this study has proven to be beneficial and suppressed systemic lupus in MRLlpr/lpr mouse model. Thus, modulating the CpG-DNA - TLR9 pathway may offer new opportunities for the understanding and treatment of lupus.