A joint venture between the Department of Biology and The Hull York Medical School

Profile

Career

Research

Overview

• Innate immune responses induced by infective larvae of Schistosoma mansoni and how these drive the polarisation of the subsequent adaptive immune response and cause immunoregulation particularly following multiple infections
• Visualisation of schistosome/immune cell interaction in the skin and lymphoid tissues using multiphoton microscopy
• Identification of ligand-pattern recognition receptor interactions involved in the recognition of schistosome molecules by cells (e.g. dendritic cells) of the innate immune response
• Proteomic definition of Th2-inducing dendritic cells
• Immunomodulation induced by chronic schistosome infection; analysis of the role of putative Th regulatory cells in the intestinal mucosa

Discoveries

• Multiple infections with S. mansoni, causes the development of immune hypo-responsiveness in the murine host resulting from the development of alternatively activated APCs, and an influx of eosinophils
• Glycan moieties on the released molecules have an important role in stimulating cytokine production by innate immune cells which in turn is dependent upon MyD88 but only partly dependent upon TLR4.
• Proteomic profiling of pro-Th2 dendritic cells reveals them to have a ‘limited’ maturation phenotype.
• CD154 has an essential role in the development of Th1 immune responses and the generation of protective immunity induced by attenuated schistosomes
• IL-10 production by CD14+ mononuclear cells is defective in patients with acne.

Current projects

• Innate Immune Responses and Immunoregulation in Schistosomiasis: Novel mechanisms in the control of infection and disease.  (EU INCO FP6 grant) Co-ordinator with 5 other partners in Ghana, Gabon, Senegal, Netherlands and Belgium.
• Immune hypo-responsiveness caused by helminth infection of the skin; regulation of dermal antigen presenting cells.  (Wellcome Trust)

Research group(s)

• Mountford research group (Immunology)

Grants

• Wellcome Trust 

Immune hypo-responsiveness caused by helminth infection of the skin (20011-2013)

Available PhD research projects

The role of helminth molecules in regulating the immune response (for 2012 - 13)

The innate immune response is believed to have a very important instructional effect upon the development and type of acquired immune response in infected hosts. In turn, we have recently discovered molecules from a parasitic helminth that down-regulate activation of the innate immune response. This project seeks to identify both the molecules from larval schistosomes (by chemical fractionation) which stimulate innate immune cells (e.g. dendritic cells and macrophages) and their receptors (Toll-like receptors, C-type lectins etc), in order to identify ligand-receptor binding connections that promote the development of Th1- or Th2-type acquired immune responses, or immune modulation. A combination of molecular (microarrays, QPCR), and cellular (flow cytometry, real time imaging, immunohistochemistry) approaches will be employed to identify receptors on host cells and changes in the profile of cytokine and cofactor expression by in stimulated cells obtained ex vivo. The project will also examine the changes in cytokine and receptor expression by in vitro-cultured accessory cells and transfected cell lines, stimulated with fractionated parasite molecules. The identified ligands then will be used to immunise experimental hosts to boost protective immunity, or reduce pathology caused by schistosome infection. No description.

Please email adrian.mountford@york.ac.uk for further enquiries.

For application requirements, process, and guidelines please see the postgraduate study pages of the Department of Biology website (http://www.york.ac.uk/biology/postgraduate/). New available studentships are announced on these web pages, the Departmental site and on FindAPhD.

Publications

Selected publications

Ward, J.S., Lynam, J.M., Moir, J.W.B., Sanin, D.E., Mountford, A.P. and Fairlamb, I.J.S. (2012) A therapeutically viable photo-activated manganese-based CO-releasing molecule (photo-CO-RM). Dalton Trans., 2012,41, 10514-10517.

Ferret-Bernard, S., Castro-Borges, W., Dowle, A.D., Sanin, D.E., Cook, P.C., Turner, J.D., MacDonald, A.S., Thomas, J.R. and Mountford, A.P. (2012). Plasma membrane proteomes of differentially matured dendritic cells identified by LC-MS/MS combined with iTRAQ labelling. Journal of Proteomics; 75, 938-948.

Paveley, R.A., Aynsley, S.A., Turner, J.D., Bourke, C.D., Jenkins, S.J., Cook, P.C., Martinez-Pomares, L., and Mountford, A.P.  (2011) The Mannose Receptor (CD206) is an important pattern recognition receptor in the detection of the infective stage of the helminth Schistosoma mansoni and modulates IFNγ production. International Journal of Parasitology  41, 1335-1345.

Meurs, L.,Labuda, L., Amoah, A.S., Mbow, M., Ngoa, U.A.,Boakye, D.A., Mboup, S., Dièye, T.N., Mountford, A.P., Turner, J.D., Kremsner, P.G., Polman, K., Yazdanbakhsh, M.,  and Adegnika, A.A. (2011) Enhanced pro-inflammatory cytokine responses following Toll-Like-Receptor ligation in Schistosoma haematobium-infected schoolchildren from rural Gabon. PLoS One 6, 9 e24393.

Turner, J.D., Jenkins, G.R., Hogg, K.G., Aynsley, S.A., Paveley,  R.A., Cook, P.C., Coles, M.C.,  and Mountford, A. P. (2011) CD4⁺CD25⁺  cells regulate colonic Th2 granulomatous pathology caused by schistosome infection.  PLoS Neglected Tropical Diseases 5, 8 e1269

Cook, P.C., Aynsley, S.A., Turner, J.T., Jenkins, G.R. an Rooijen, N. Leeto, M., Brombacher, F., and Mountford, A. P. (2011). Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells.  PLoS Pathogens 7, 3, e1001323

Caillon, F., Eady, E.A., O’Connell, M., Jenkins, G.R., Cove, J.H., Layton, A.M., and Mountford, A.P. (2010) IL-10 secretion by CD14⁺ peripheral blood mononuclear cells induced by Propionibacterium acnes is down regulated in patients with acne vulgaris.  British Journal of Dermatology 162, 296-303.

Paveley, R.A, Aynsley, S.A., Cook, P.C., Turner, J.D., and Mountford, A.P. (2009) Fluorescent imaging of antigen released by a skin-invading helminth reveals differential uptake and activation profiles by antigen presenting cells. PLoS Neglected Tropical Diseases 3, e528

Ferret-Bernard, S. F. Curwen, R.S, and Mountford, A. P. (2008) Proteomic profiling of Th2 inducing dendritic cells stimulated with helminth products.  Proteomics 8: 980-993.

Kumkate, S., Jenkins, G.R., Paveley, R.A., Hogg, K.G. and Mountford, A. P. (2007) CD207⁺ Langerhan’s cells migrate to the draining lymph nodes after exposure to Schistosoma mansoni but they are not the major antigen presenting cell population. International Journal of Parasitology 37: 209-220.

Hewitson, J.P., Hamblin, P.A. and Mountford, A.P. (2007) In the absence of CD154, administration of IL-12 restores Th1 responses but not protective immunity to Schistosoma mansoni. Infection and Immunity 75: 3539-3547.

Hewitson, J.P., Jenkins, G.R., Hamblin, P.A. and Mountford, A.P. (2006) CD40/CD154 interactions are required for the optimal maturation of skin-derived APCs and the induction of helminth-specific IFNg but not IL-4.  Journal of Immunology 177: 3209-3217.

Jenkins, S.J and Mountford, A.P. (2005)  Dendritic cells activated with products released by schistosome larvae drive Th2-type responses that can be inhibited by manipulation of CD40 costimulation.   Infection and Immunity 73: 395
Jenkins, S.J. Hewitson, J.P. Ferret-Bernard, S. and Mountford, A.P. (2005) Schistosome larvae stimulate macrophage cytokine production through TLR4-dependent and independent pathways.  International Immunology 17: 1409-1418.

Jenkins, S.J. Hewitson, J.P. Jenkins, G.R and Mountford, A.P. (2005) Modulation of the host’s immune response by schistosome larvae.  Parasite Immunology 27: 385-393.

External activities

Memberships

• Member of the British Society for Immunology
• Member of the British Society for Parasitology

Editorial duties

• Editorial Review Board: Parasite Immunology