Technological advances in understanding host responses to parasites and parasite manipulation of host responses

Welwyn Garden City , Hertfordshire
Friday, 29 June 2007

Technological advances in understanding host responses to parasites and parasite manipulation of host responses
Friday, 29 June 2007 09:00 - 17:00

BioPark Hertfordshire
Broadwater Road
Welwyn Garden City
Hertfordshire
AL7 3AX
United Kingdom

Map and Directions

09:00 – 09:45 Registration - Tea/Coffee

09:45 – 10:00 Introduction by the Chair: Dr. Alasdair Nisbet, Moredun Research Institute, Scotland

10:00 – 10:30 Costimulatory requirements for dendritic cell induction of theTh2 response to schistosomes. Dr. Stephen Jenkins, Institute of Immunology and Infection Research University of Edinburgh, Scotland
Priming and expansion of polarised T-helper (Th) cell responses requires a series of co-stimulatory interactions between Th cells, antigen presenting cells and a network of other cells. Helminth infections are associated with strong induction of Th2 responses, and we have previously shown that exposure of dendritic cells (DC) to Schistosoma mansoni soluble egg antigen (SEA) conditions them to drive Th2 responses in vivo. Using both infection and DC models of Th2 induction, we have established a hierarchy of co-stimulatory requirements for induction of Th2 responses, and have addressed the cellular sources and mechanisms downstream of these molecules in vivo.

10:30 – 11:00 Schistosome immunology: proteins to populations
Dr
Francisca Mutapi, University of Edinburgh, UK
Using a proteomic approach we have conducted the most comprehensive characterisation of Schistosoma haematobium antigens to date and describe several novel antigens for all schistosome species. In addition we have used a genomic approach to identify a novel tegumental (Sh13) and express it as a recombinant protein for our experimental and human studies. We have used quantitative work to show that human anti-Sh13 antibody responses are associated with resistance to infection. This talk will demonstrate how we integrate a successful programme of fieldwork, epidemiology, state-of–the-art molecular biology and immunology for a better understanding of the nature and development of schistosome-acquired immunity in human populations.

11:00 – 11:30 Morning Tea/Coffee and Poster Viewing

11:30 – 12:00 The therapeutic potential of the filarial nematode-derived immunomodulator, ES-62
Professor William Harnett,
University of Strathclyde, UK
We have characterised a major filarial nematode secreted glycoprotein, ES-62. Mediated in part through unusual post-translational addition of phosphorylcholine to an N-type glycan, ES-62 has been found to modulate immune cell signal transduction pathways resulting in a broad range of immunomodulatory effects that are in general, anti-inflammatory. A consequence of this is that ES-62 is able to ameliorate inflammation in rodent models of human diseases such as autoimmune and allergic disorders. ES-62 thus represents the starting point in the development of novel drugs for certain human diseases that are associated with aberrant immune responses.

12:00 – 12:30 The Release of the Malaria Parasite and the transfer of the DIIC(16) (3) from infected erythrocytes to intracytoplasmatic membrances,
Gladys Thalia Cortés, Investigador -Docente Dedicación exclusiva, Columbia
The merozoite release from the infected erythrocyte and the membranes participing in parasite exit is controversial. The problem faced includes the difficulty in studying this phenomenon. This Talk will focus on describe the observations when a highly synchronized population of Plasmodium falciparum–infected erythrocytes was studied by electron microscopy during the period of merozoite release and reinvasion. The fate of the erythrocyte membrane was examined by labeling with the fluorescent lipid probe 1, 1’-dihexadecyl-3-3'-3-3'- tetramethylindocarbocyanine (diIC16) and followed by photoconversion. In the case of Leishmania parasite the exit of the parasite from the infected macrophages was studied by capacitance measurements.

12:30 – 13:00 Group and speakers photo and then*Tour of the BioPark

13:00 – 14:00 Lunch and Poster Viewing

14:00 – 14:30 The hunt for malaria-specific B cells and plasma cells
Dr. Emma Cadman, The Royal Veterinary College, UK
Tracking of antigen-specific T cells by flow cytometry is now relatively well established, however identifying antigen-specific B cells by this method is trickier. We attempted to track malaria-specific B cells throughout infection using a fluorescently labelled recombinant malaria protein. Here we outline the methods used, the pros and cons of this approach and the results we obtained.

14:30 – 15:00   “Friendly Fire” – Investigating the role of eosinophils in protection and pathology
Dr Rachel Lawrence, Royal Veterinary College, University of London
Eosinophils play a protective role against primary infections with microfilariae of the parasitic nematode, Brugia malayi. Interestingly, the rapid clearance of a secondary microfilarial infection is not dependent on eosinophil presence. Blood eosinophil peroxidase levels are raised in primary, but not secondary infection while eosinophils degranulate in the lung during secondary infection. This suggests that differences in eosinophil degranulation are important for microfilarial clearance. We are using a variety of techniques to investigate phenotypic differences between eosinophils that are protective and those that are pathogenic.

15:00 – 15:30 Afternoon Tea/Coffee and Last Poster Viewing

15:30 – 16:00 The use of proteomics and transcriptomics to understand the host response to intestinal nematode infection
Dr Alan Pemberton, University of Edinburgh, Division of Veterinary Clinical Sciences, Scotland
We used proteomics and transcriptomics to investigate the intestinal response to Trichinella spiralis infection in BALB/c mice. Microarrays detected increases in a number of goblet cell and mast cell specific gene transcripts, and down regulation of tight junction elements. There was also novel expression of a2,3-sialyltransferase, small proline rich protein 2A and resistin-like molecule-b. Proteomic approaches also indicated very strong upregulation of intelectin-2 and phospholipase A2, Group 4C, neither of which were present on the array. These findings are consistent with Th2 regulated expression of mucosal effector molecules in the intestinal epithelium.

16:00 – 16:30 
Development of a novel model to study infectious diseases
Dr Naveed Khan, Birkbeck, University of London
For the first time, we have shown that locusts can be used as a model to study E. coli K1 pathogenesis. E. coli K12 strain HB101 has very low pathogenicity to locusts and does not invade the locust brain, whereas injection of 2 x 106 E. coli K1 strain RS218 (O18:K1:H7) kills almost 100% of locusts within 72 h, and invades the brain within 24 h of injection. Both mortality and invasion of the brain in locusts after injection of E. coli K1 require at least two of the known virulence determinants shown for mammals. Thus, deletion mutants that lack OmpA (Outer membrane protein A) or CNF1 (cytotoxic necrotizing factor 1) have reduced abilities both to kill locusts and invade the locust brain compared with the parent E. coli K1. The likely existence of additional virulence determinants as well as the host factors can be investigated in vivo using this insect system.

17:00 Chairman’s summing up & close.



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