Prof Andrew Macdonald

Andrew Macdonald – Research summary

Prof Andrew MacDonald

Prof Andrew MacDonald

The research in my laboratory investigates how pathogen interaction with the innate immune system influences the development of adaptive immunity and inflammation. My particular interest is Type 2 inflammation, which is responsible for widespread suffering in allergy, as well as being a hallmark of infection with parasitic helminths. Our work addresses some outstanding fundamental questions about the role of dendritic cells (DCs) in orchestration of Type 2 inflammation. DCs are centrally involved in initiation of immune responses in most settings, but the precise mechanisms by which they direct Type 2 inflammation are currently not known.

The main questions we are addressing at the moment are:

  1. How do DCs become activated in Type 2 settings?
  2. How necessary are DCs for induction and coordination of Type 2 inflammation?
  3. By what mechanism do DCs initiate Type 2 inflammation?

Our research uses a combination of in vivo and in vitro model systems, focusing on the Type 2 response to the medically important parasitic helminth Schistosoma mansoni. Murine infection with this parasite provides a relevant experimental model of Type 2 inflammation that has been used extensively by my laboratory and others to reveal important cellular and molecular players and processes during hepatic, intestinal and pulmonary inflammation. Since moving to Manchester, we also have developed substantial expertise in analysis of human and murine pulmonary inflammation, in particular against house dust mite and fungal allergens. The overarching aim of our research is to determine how Type 2 immunity is initiated, maintained and regulated, with the ultimate goal being identification of cellular and molecular targets for rational development of therapeutics.

Email: andrew.macdonald@manchester.ac.uk Tel: 0161 275 1504


People

Andrew Macdonald – People

Alex Phythian-Adams (Postdoc)
Dennis Au
Sheila Brown (RA)
James Crooks (Postdoc)
Cecilia Forss (PhD student)
Alicia Galdon
Emma Houlder (PhD student)
Amanda Ridley
Freya Svedberg (PhD student)


People

Andrew Macdonald – People

Alex Phythian-Adams (Postdoc)
Dennis Au
Sheila Brown (RA)
James Crooks (Postdoc)
Cecilia Forss (PhD student)
Alicia Galdon
Emma Houlder (PhD student)
Amanda Ridley
Freya Svedberg (PhD student)


Collaborators

The University of Manchester

Richard Grencis
Judi Allen
Peter Cook
Matt Hepworth
Kathryn Else
Dave Thornton
Kevin Couper
Angela Simpson
Tracy Hussell
Dan Davis
Mark Travis
John Grainger
Kostas Kostarelos
Nicola Tirelli

Farther afield:

Adrian Bird, University of Edinburgh
Simon Milling, University of Glasgow
Karl Hoffman, University of Aberystwyth
Matt Berriman, Sanger Institute
Ben Dewals, University of Liege
Franca Ronchese, Malaghan Institute
Rose Maciewicz, Danen Cunoosamy and Malin Enerback: AstraZeneka
Edith Hessel, Soren Beinke, Paul Redford, Antoon van Oosterhout and Matt Edwards: GSK

Biography

I completed my PhD studying immunity to helminth parasites at the University of Edinburgh in 1998. After several years in the U.S., first at Cornell University and then at the University of Pennsylvania, I returned to the UK in 2002 to the University of Edinburgh where I established my lab through successive MRC Career Development and Senior Fellowships at the Institute of Immunology and Infection Research. In January 2013 I took up the position of Professor of Immunology at the Manchester Collaborative Centre for Inflammation Research (MCCIR).

Selected publications

  • Rachel J. Lundie, Lauren M. Webb, Angela K. Marley, Alexander T. Phythian-Adams, Peter C. Cook, Lucy H. Jones, Sheila Brown, Rick M. Maizels, Louis Boon, Meredith O’Keefe and Andrew S. MacDonald. A central role for hepatic conventional dendritic cells in supporting Th2 responses during helminth infection. 2016. Immunology and Cell Biology. 94:400-410.
  • Lucy H. Jones, Peter C. Cook, Al C. Ivens, Graham D. Thomas, Alexander T. Phythian-Adams, Judith E. Allen and Andrew S. MacDonald. Modulation of dendritic cell alternative activation and function by the vitamin A metabolite retinoic acid. 2015. International Immunology. 11: 589-596.
  • Toshifumi Fujimori, Aleksander M. Grabiec, Manminder Kaur, Thomas J. Bell, Naoya Fujino, Peter C. Cook, Freya R. Svedberg, Andrew S. MacDonald, Rose A. Maciewicz, Dave Singh and Tracy Hussell. The Axl receptor tyrosine kinase is a discriminator of macrophage function in the inflamed lung. 2015. Mucosal Immunology. 8: 1021-1030.
  • Peter C. Cook, Heather Owen, Aimee M. Deaton, Jessica G. Borger, Sheila L. Brown, Thomas Clouaire, Gareth-Rhys Jones, Lucy H. Jones, Rachel J. Lundie, Angela K. Marley, Vicky L. Morrison, Alexander T. Phythian-Adams, Elizabeth Wachter, Lauren M. Webb, Tara E. Sutherland, Graham D. Thomas, John R. Grainger, Jim Selfridge, Andrew N.J. McKenzie, Judith E. Allen, Susanna C. Fagerholm, Rick M. Maizels, Alasdair C. Ivens, Adrian Bird and Andrew S. MacDonald. A dominant role for the methyl-CpG binding domain protein Mbd2 in controlling Th2 induction by dendritic cells. 2015. Nature Communications. 6: 6920.
  • Vicky L. Morrison, Martyn J. James, Katarzyna Grzes, Peter Cook, David G. Glass, Hwee San Lek, Christian Gawden-Bone, Colin Watts, Owain R. Millington, Andrew S. MacDonald and Susanna C. Fagerholm. Loss of beta2-integrin-mediated cytoskeletal linkage reprogrammes dendritic cells to a mature migratory phenotype. 2014. Nature Communications. 5: 5359.
  • Aimee M. Deaton, Peter C. Cook, Dina De Sousa, Alexander T. Phythian-Adams, Adrian Bird and Andrew S. MacDonald. A unique DNA methylation signature defines a population of IFN-γ and IL-4 double-positive T cells during helminth infection. 2014. European Journal of Immunology. 44: 1835-1841.
  • Anna M. Hoy, Rachel J. Lundie, Al Ivens, Juan F. Quintana, Norman Nausch, Thorsten Forster, David W. Dunne, Francisca Mutapi, Andrew S. MacDonald and Amy H. Buck. Parasite-specific microRNAs in host serum as novel biomarkers of helminth infection. 2014. PLoS Neglected Tropical Diseases. 8: e2701.
  • Rachel E. Rigby, Lauren M. Webb, Karen J. Mackenzie, Yue Li, Andrea Leitch, Martin A.M. Reijns, Rachel J. Lundie, Ailsa Revuelta, Donald J. Davidson, Sandra Diebold, Yorgo Modis, Andrew S. MacDonald and Andrew P. Jackson. RNA:DNA hybrids are a novel molecular pattern sensed directly by TLR9. 2014. EMBO Journal. 33: 542-548.
  • Peter C. Cook, Lucy H. Jones, Stephen J. Jenkins, Thomas A. Wynn, Judith E. Allen and Andrew S. MacDonald. Alternatively activated dendritic cells regulate CD4+ T cell polarization in vitro and in vivo. 2012. P.N.A.S. 109: 9977-9982.
  • Georgia Perona-Wright, Rachel J. Lundie, Stephen J. Jenkins, Lauren M. Webb, Richard K. Grencis and Andrew S. MacDonald. Concurrent bacterial stimulation alters the function of helminth activated dendritic cells, resulting in IL-17 induction. 2012. Journal of Immunology. 188: 2350-2358.
  • Stephen J. Jenkins, Dominik Ruckerl, Peter C. Cook, Lucy H. Jones, Fred D. Finkelman, Nico van Rooijen, Andrew S. MacDonald and Judith E. Allen. 2011. Local macrophage proliferation, rather than recruitment from the blood, is a signature of Th2 inflammation. Science. 332: 1284-1288.
  • Alexander T. Phythian-Adams, Peter C. Cook, Rachel J. Lundie, Lucy H. Jones, Katherine A. Smith, Tom A. Barr, Kristin Hochweller, Gunter J. Hammerling, Stephen M. Anderton, Rick M. Maizels and Andrew S. MacDonald. 2010. CD11c depletion severely disrupts Th2 induction and development in vivo. Journal of Experimental Medicine. 207: 2089-2096.
  • Georgia Perona-Wright, Stephen J. Jenkins, Richard A. O'Connor, Dimitris Zienkiewicz, Henry J. McSorley, Rick M. Maizels, Stephen M. Anderton and Andrew S. MacDonald. 2009. A pivotal role for CD40-mediated IL-6 production by dendritic cells during Th17 induction in vivo. Journal of Immunology. 182: 2808-2815.
  • Andrew S. MacDonald and Rick M. Maizels. 2008. Alarming dendritic cells for Th2 induction. Journal of Experimental Medicine. 205: 13-17.
  • Stephen J. Jenkins, Georgia Perona-Wright and Andrew S. MacDonald. 2008. Full development of Th2 immunity requires both innate and adaptive sources of CD154. Journal of Immunology. 180: 8083-8092.
  • Georgia Perona-Wright, Stephen J. Jenkins and Andrew S. MacDonald. 2006. Dendritic cell activation and function in response to Schistosoma mansoni. International Journal for Parasitology. 36(6): 711-721.
  • Edward J. Pearce and Andrew S. MacDonald. 2002. The Immunobiology of Schistosomiasis. Nature Reviews Immunology. 7: 499-511.
  • Rachel E. Rigby, Lauren M. Webb, Karen J. Mackenzie, Yue Li, Andrea Leitch, Martin A.M. Reijns, Rachel J. Lundie, Ailsa Revuelta, Donald J. Davidson, Sandra Diebold, Yorgo Modis, Andrew S. MacDonald and Andrew P. Jackson. 2014. RNA:DNA hybrids are a novel molecular pattern sensed directly by TLR9. EMBO Journal. 33: 542-548.