March 2014 Lab of the Month - Taylor Lab
Matt Taylor is a lecturer in the Institute of Immunology and Infection Research at the University of Edinburgh. His group focuses on the initiation and maintenance of effector and regulatory T cell responses during chronic parasitic infections.
Matt orignally came to Edinburgh as an undergraduate student in Immunology. He then left Edinburgh for a while, first to study for his PhD at the University of Manchester and then to carry out postdoctoral work at the University of British Columbia. Matt returned to Edinburgh in 2001, initially continuing as a postdoctoral fellow and then obtaining an MRC Career Development Fellowship in 2006-2012. Most recently Matt was been awarded an MRC New Investigator Research Grant to continue his work.
About the research currently on-going in his lab Matt says:
The key to immunity is communication; immune cells constantly talk to each other. In the absence of infection or disease this is to check that all is well. If a foreign body is detected these conversations decide whether an immune response is needed... A fascinating aspect of parasites is that they have learnt the immune system’s language, surviving within the host by manipulating immune conversations. They can disrupt immune signals hindering immune activation, and can send conflicting signals that change the type of immune response or even turn it off.
We are interested in how the immune system communicates during infection, and believe that by studying the way parasites influence immune responses we can learn how to control immunity. This will allow us to either promote protective immunity through vaccines, or turn off inappropriate immune responses such as those responsible for autoimmunity or allergies.
Examples of parasitic helminths and their consequences in human health. Left: an example of the parasitic worms Litomosoides sigmodontis Matt uses in his research - adult females live in lymphatics (in humans) and release filariae which then make their way into the blood stream. Middle: group of women suffering from elephantiasis, caused by infection with filarial worms such as Brugia malayi which have blocked the flow of lymph around the body, resulting in chronic oedema of the lower extremities. Right: child affected by onchocerciasis (river-blindness), following infection by the filarial parasite Onchocerca volvulus.
Projects on-going in the Taylor lab.
Th2 cell-intrinsic hypo-responsiveness - how helminths turn off the host immune responses
The Taylor lab has previously demonstrated that the effector T cells usually responsible for coordinating the immune response to kill helminths (CD4+ Th2 cells) become non-functional during long-term infection. This represents a novel form of immunological tolerance (referred to as Th2 cell-intrinsic hypo-responsiveness), and its development is a key element defining host susceptibility to infection. Johanna Knipper, a postdoc in the lab, is now leading the work to identify the molecular mechanisms of this cell-intrinsic hypo-responsiveness, with the overall goal of being able to therapeutically switch Th2 cells between active and inactive states. In this way they (1) hope to counter Th2 cell dysfunction during helminth infections thereby promoting protective immunity, and (2) learn how to turn off the Th2 cells that cause allergic inflammation.
Foxp3+ Regulatory T cells
The second main interest in the lab is the activity of a particular subset of regulatory T cells called Foxp3+ Treg cells. Work in the lab has shown that these Foxp3+ Tregs respond remarkably rapidly to filarial parasites, and by doing so inhibit protective immunity in the host. They are now continuing work that has shown that targeting these Foxp3+ Tregs is a potential therapeutic strategy for restoring immunity to explore how this might be achieved.
Co-infections and transgenic mice
In addition to these major projects the Taylor lab is collaborating with Gareth Hardisty in Bernadette Dutia's lab at the Roslin Institute on a study to understand how and if co-infection of mice with Litomosoides sigmodontis protects against pathology upon infection with influenza virus. Matt is also working with Taconic.com on a project funded by the University's Institutional Strategic Support Fund to generate constitutive IL-4-Cre and inducible IL-4-CreERT2 transgenic mice. These will allow the tracking and fate mapping of IL-4 secreting Th2 cells, as well as provide the ability to specifically delete genes within IL-4 secreting cells.
Find out more about work in the Taylor lab
- Watch his Research in a Nutshell video, where he talks about his current work into how parasitic helminths are able to turn off host immune responses.
- Visit the lab website: http://taylor.bio.ed.ac.uk
Outside the lab - lecturing and course organisation
In addition to his work in the lab Matt is very active as a lecturer to third and fourth year Immunology undergraduates, and he is the course organiser of the Micro-organisms, Cells and Immunity course for second year students. And if all that is not enough he has also volunteered to organise the 2014 British Society of Immunology summer school which will see 80 students descending on Edinburgh from 1-4 July for 4 days of intensive study. If you would like more information about the summer school, please click here.
Some recent publications from the Taylor lab:
- van der Werf, N., Redpath, S.A., Azuma, M., Yagita, H., and Taylor, M.D. (2013): Th2-Th2 cell-intrinsic hypo-responsiveness determines susceptibility to helminth infection. PLoS Pathog. 9:e1003215
- This paper was featured in an Edinburgh Infectious Diseases news story
- Redpath, S.A., van der Werf, N., Cervera, A.M., MacDonald, A.S., Gray, D., Maizels, R.M., and Taylor, M.D. (2013): ICOS controls Foxp3+ regulatory T-cell expansion, maintenance and IL-10 production during helminth infection. Eur. J. Immunol. 43:705-715
- Taylor, M.D., van der Werf, N., and Maizels, R.M. (2012): T cells in helminth infection: the regulators and the regulated. Trends Immunol. 33:181-189
- van der Werf, N., Redpath, S.A., Phythian-Adams, A.T., Azuma, M., Allen, J.E., Maizels, R.M., MacDonald, A.S., and Taylor, M.D. (2011): Th2 responses to helminth parasites can be therapeutically enhanced by, but are not dependent upon, GITR-GITR ligand costimulation in vivo. J. Immunol. 187:1411-1420
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