The 2013 three Rs Event - 19th September 2013

The 2013 three Rs Event: Toll like receptors (TLRs),RIG-like receptors (RLRs) and Nod-like receptors (NLR)

Thursday, 19 September 2013

The aim of this meeting is to provide an overview of these three families of receptors and provide the most recent advances in the area of innate immune pattern recognition

Meeting chairs: Dr Martha Triantafilou/Professor Kathy Triantafilou, Cardiff University School of Medicine, UK

This event has CPD accreditation and will have a troubleshooting panel session.
On registration you will be able to submit your questions to the panel that will be asked by the chair on the day of the event.

9:00 – 9:45 Registration

9:45 – 10:00 Introduction by the Chairs: Dr Martha Triantafilou/Professor Kathy Triantafilou, Cardiff University School of Medicine, UK

10:00 – 10:30 Pattern recognition receptor in Gram-negative intracellular infections: friends or foes?

Dr Pietro Mastroeni, Cambridge University, UK

Pattern recognition receptors are important for the expression of immunity to bacterial infection and modulate aspects of the development of acquired immunity. However in some cases their stimulation can lead immune paralysis and to suppression of the host response.

10:30 – 11:00 Transcriptome analysis of cigarette smoke extract induced TLR2-dependent activation of human cells.

Dr Mark Paul-Clark, National heart and Lung Institute, London, UK

Smoking cigarettes causes approximately 5 million deaths world wide each year, and is a risk factor for a number of chronic diseases. We have previously shown that oxidants and cigarette smoke extract (CSE) activate cells in vitro and in vivo, in part via the pattern recognition receptor TLR2. We transfected HEK293 cells with TLR2/6 or control vector were treated with H2O2, CSE and control media for 8h. Expression patterns in HEK293 cells were similar to those obtained from THP-1 cells and PBMCs. Pathway analysis of these cells revealed that inflammation was associated with NRF2-mediated and aryl hydrocarbon receptor signaling pathways.

11:00 – 11:30 Speakers’ photo then mid-morning break and trade show

Please try to visit all the exhibition stands during your day at this event. Not only do our sponsors enable Euroscicon to keep the registration fees competitive, but they are also here specifically to talk to you

11:30 – 12:00 Ruminant livestock toll-like receptors: informing TLR evolution and function.

Professor David Haig, School of Veterinary Medicine and Science, Nottingham University, UK

There are ~1400 breeds of sheep and 1300 breeds of cattle through domestication (around 10,000 years ago). Artificial selection for specific traits accelerated around 200 years ago. Consequently, this provides an opportunity to study TLR evolution and function in a distinct group of mammals closely associated with man. We have studied TLRs 2 and 5 in particular. In TLR5, we identified positive selective pressure in the domesticated ruminant clade suggesting rapid diversifying selection compared to other mammals. Stop codon variants of bovine TLR5 may indicate an alternative function. These and other examples of TLR variation will be presented.

12:00 – 12:45 Oral Presentations

12:00 – 12:15 INFLAMMATORY RESPONSE TO FOOTROT IN SHEEP

R. Davenport, C. Haewood, M. Baker and S. Tötemeyer

School of Veterinary Medicine and Science, University of Nottingham, Loughborough, LE12 5RD, UK.

12:15 – 12:30 THE ROLE OF TOLL-LIKE RECEPTOR 2 AND 4 IN BEHÇET’S DISEASE PATHOGENESIS

N Seoudi1, L A Bergmeier1, E Hagi-Pavli1, D Bibby2, M A Curtis2 and F Fortune1

1Centre for Clinical and Diagnostic Oral Sciences. Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom.2Centre for Immunology and Infectious Diseases, The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom

12:30 – 12:45 CHOLESTEROL OXIDASE OF MYCOBACTERIUM TUBERCULOSIS AFFECTS THE TOLL-LIKE RECEPTOR 2-MEDIATED SIGNALING PATHWAY IN HUMAN MACROPHAGES

Klink M, Brzezinska M, Szulc I, Brzostek A, Kielbik M, Dziadek J

Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106 Str. 93-232 Lodz, Poland

12:45 – 13:45 Lunch and trade show

Please try to visit all the exhibition stands during your day at this event. Not only do our sponsors enable Euroscicon to keep the registration fees competitive, but they are also here specifically to talk to you.

13:45 – 14:45 Question and Answer Session

Delegates will be asked to submit questions to a panel of experts. Questions can be submitted before the event or on the day.

14:45 - 15:15 Talk title to be confirmed

Professor Dirk Werling, Dept. of Pathology and Infectious Diseases, Royal Veterinary College, UK

15:15 – 15:45 Afternoon Break

15:45 – 16:15 Connecting innate immunity to autoimmunity

Dr Sandra Sacre, Brighton and Sussex Medical School, UK

Growing evidence suggests that TLRs, may contribute to the pathogenesis of many autoimmune diseases. Initially TLRs were identified by their ability to recognise pathogens, but it was later discovered that they also recognise endogenous ligands present at sites of inflammation or tissue damage. This ability to respond to endogenous molecules has made the TLRs promising candidates to explain the presence of chronic inflammation in the absence of an infection. A role for TLRs in autoimmunity may be due to changes in their expression, function and/or downstream regulation. This presentation will focus on data exploring the possible connections between TLR signalling and sustained inflammation in rheumatoid arthritis.

16:15 – 16:45 Pattern Recognition Receptor recognition of bacterial infection: are all animals created equal?

Dr Clare Bryant, University of Cambridge, UK

16:45 - 17:00 Chairman’s summing up

About the Chairs:

Over the past few years the Triantafilou group has been focusing on unravelling the molecular mechanisms behind the innate recognition of bacterial as well as viral pathogens. In particular, we have focused on the involvement of the Toll like receptor (TLR) family of proteins, a recently identified family of pattern recognition receptors (PRRs), in the innate immune sensing. We have the expertise and the research tools for investigating receptor interactions using bioimaging techniques, such a Fluorescence Resonance Energy Transfer (FRET), Fluorescence Recovery after Photobleaching (FRAP), Single Particle Imaging (SPFI), Single Particle Tracking (SPT), Fluorescent Loss in Photobleaching (FLIP) as well as live cell imaging. Using combinations of these techniques, our group has discovered novel concepts in innate immune recognition of microbial ligands by TLRs and co%operating PRRs. We have been one of the first to demonstrate that the single%receptor concept of innate immune recognition is an oversimplified one and that different combinational associations of receptors determine the innate immune response to different microbial pathogens, using a range of non%invasive biophysical techniques. We performed several studies investigating associations of PRRs in response to bacterial products from Helicobacter pylori,Neisseria meningitidis, and bacterial lipopeptides. Furthermore, we demonstrated that membrane microdomains, or “lipid rafts” play an important role in this receptor cluster formation by providing a microenvironment for these interactions to take place. This was the first ever publication demonstrating that TLRs exist and signal within lipid rafts (making this paper one of the most cited papers in the field). We provided the first dynamic picture of TLR engagement by their ligand by determining the lateral diffusion of receptors involved in the innate immune response before and after stimulation by bacterial products . It has helped us understand the organisation, lateral mobility and confinement of PRRs involved in the innate immune response on the plasma membrane. In addition, using fluorescent imaging, we have revealed that TLR2 exists as a heterodimer prior to ligand engagement, as well as its intracellular trafficking and targeting in response to Gram%positive bacterial products. More recently, we have demonstrated that CXCR4 acts as a negative regulator for TLR2 and its significance in the innate recognition of Porphyromonas gingivalis (Hajishengallis et al. 2008). This was the first study demonstrating that TLR2%CXCR4 association can impair innate immune responses. Finally, we have shown that TLR4, TLR7 and TLR8 are involved in sensing viral products. These were the first studies to reveal how enteroviruses are recognised by the innate immune system

About the Speakers:

David Haig is currently studying innate immunity and virus pathogenesis and control in livestock animals at the new Veterinary School at the University of Nottingham. He graduated from the University of Glasgow with a B.Sc. in Biochemistry and an M.Sc. and Ph.D. from studying the immunology of nematode infections and mast cell biology. He spent a few years at the WHO Immunology Research and Training Centre at the Instituto Butantan, Sao Paulo, Brazil where he set up a Parasitology laboratory and studied immunity to helminth parasites in rodents. He joined the Moredun Research Institute in 1985 and became Head of Immunology then Head of the Division of Virology before leaving for Nottingham in 2007.

Katrin Rittinger obtained a degree in chemistry from the University of Heidelberg, Germany. She then went on to do a Ph.D. at the Max Planck Institute for Medical Research in Heidelberg in the group of Roger Goody, characterising the nucleotide and oligonucleotide-binding properties of HIV reverse transcriptase and the mechanism of action of non-nucleoside RT inhibitors. After a short postdoctoral period at the Max Planck Institute for Molecular Physiology in Dortmund, Germany, she came to NIMR in 1996 for a second postdoc, working on the structural characterisation of 14-3-3 ligand complexes and the regulation of Rho family GTPases. In 2000 she established her own research group and has since studied a number of protein assemblies that regulate different aspects of signal transduction using biochemical and structural methods. In addition, the group collaborates with other Divisions at NIMR to extend the experimental approaches available to answer a given biological question.

Mark Paul-Clark is an accomplished researcher with a number of publications in leading journals. He has established a track record in attracting independent funding and contributes significantly to both postgraduate and undergraduate teaching. Dr Paul-Clark’s research focuses upon understanding the process of inflammation with a particular interest in oxidants and the damage they cause. Most recently he has concentrated his research into the area of pattern recognition receptors and inflammation. He completed his PhD with Professor Derek Willoughby before joining Professor Roderick Flower and Professor Mauro Perretti for his postdoctoral training. In 2002 Dr Paul-Clark Joined Professor Jane Mitchell’s group to study the role of pattern recognition receptors, including Toll like receptors, in inflammation. Since this time Dr Paul-Clark was awarded a Research Fellowship from the British Lung Foundation and a University award from the Wellcome Trust, with which he will take up an academic lectureship position within Cardiothoracic Pharmacology.

Clare Bryant - 1985 BSc (Hons) Biochemistry and Physiology, University of Southampton, 1989 BVetMed, University of London,1992 PhD, University of London. 1992%1995 Wellcome Trust Veterinary Research Training Fellowship, sRoyal Veterinary College, University of London, 1995%1996 Research Scientist, William Harvey Research Institute, London, 1996 -2000 Wellcome Trust Research Career Development Fellow and 2000%2003 Wellcome Trust Research Advanced Fellow, Department of Clinical Veterinary Medicine, The University of Cambridge, 2003%University Lecturer and Senior Lecturer in Clinical Pharmacology, Department of Veterinary Medicine, The University of Cambridge. Research Interests: Role of Pattern Recognition Receptors (PRRs) in bacterial infection; species specificity in PRR activation.

Pietro Mastroenis’ is a Reader at the University of Cambridge. He obtained a Degree in Medicine and Surgery at the Univerisity of Messina, Italy prior to moving to the UK where he obtained a PhD at the Department of Pathology of the University of Cambridge and worked as a postdoctoral Fellow at Imperial College, London. His research has established several landmarks in the fields of pathogenesis of bacterial infections, immunity, immunoevasion and vaccine development. His research group is currently pioneering the use of innovative multidisciplinary approaches towards a global understanding of infection dynamics in the face of immunity and vaccination.

Paul-Clark completed his PhD with Professor Derek Willoughby before joining Professor Roderick Flower and Professor Mauro Perretti for his postdoctoral training. In 2002 Dr Paul-Clark Joined Professor Jane Mitchell’s group to study the role of pattern recognition receptors, including Toll like receptors, in inflammation. Since this time Dr Paul-Clark was awarded a Research Fellowship from the British Lung Foundation and a University award from the Wellcome Trust, with which he will take up an academic lectureship position within Cardiothoracic Pharmacology.

Sandra Sacre received her PhD in Physiology from University College London in 2000. Sandra then spent one year working at the Royal Free Hospital (University College London) before moving to the Kennedy Institute of Rheumatology (Imperial College London) to work on toll-like receptors in rheumatoid arthritis. In 2009, Sandra moved to Brighton and Sussex Medical School (University of Sussex) where she is currently a Senior Lecturer in Molecular Cell Biology. Sandra Sacre’s research is focused on the role of innate immunity in musculoskeletal diseases including rheumatoid arthritis and systemic lupus erythamatosus.

Keywords: Innate Immunity, DNA sensing, Inflammasome, Type I interferon, RLHs, TLRs, Interferon, rhinovirus, asthma, TLR4, rhinovirus, LPS, TLR, signal transduction, scaffold complexes, NLR, PRR, LPS, Salmonella, Innate Immunity, atherosclerosis, NLRP3, Inflammasome, IL1, infection, immunity TLRS, bacteria, Oxidants, TLRs, Bioinformatics and transcripome, TLR2, TLR5, ovine, bovine, evolution, Autoimmunity, inflammation, toll-like receptors, rheumatoid arthritis, cytokines

Registration Web Site: www.regonline.co.uk/TOLL2012

Post expires at 8:36am on Thursday September 19th, 2013

Bookmark It