Dr Elizabeth Mann

Elizabeth Mann – Research summary

Dr Elizabeth Mann

Dr Elizabeth Mann

Macrophages are crucial components of the intestinal immune system where they are highly specialized to recognize and respond to the trillions of harmless bacteria in the gut without provoking an inflammatory response. The importance of this pathway is highlighted by the damage caused when this process breaks down, leading to inflammatory bowel disease (IBD). IBD is a common, debilitating condition with rapidly increasing incidence throughout the developed world and is a significant global, economic and public health burden. Inflammatory macrophages accumulate in the inflamed intestines in IBD with pathology driven by CD4+ T-cell responses against the gut microbiota. The mechanisms by which intestinal macrophages normally become conditioned to promote microbial tolerance are unclear, although strong epidemiological evidence linking disruption of the gut microbiota by antibiotic use to IBD indicates an important role for the gut microbiota in modulating intestinal immunity.

Gut lumen in health and disease

My research programme focuses on understanding how the gut microbiota shapes intestinal macrophage function to educate the adaptive immune system long-term to avoid pathogenic T-cell responses against the microbiota. The aims of my research are to unravel the cellular and molecular pathways by which the gut microbiota controls macrophage function, not only in the intestine but at other antigen-rich mucosal sites such as the lung. Specifically, I am using antibiotics to disrupt the intestinal microbiota with profound effects on macrophage-mediated T-cell immunity, susceptibility to Th17 and Th2 mediated mucosal infections and on the composition of bacterial communities in the intestine. I will also be investigating critical windows of development during which macrophage function is shaped by the microbiota and narrowing down bacterial groups, microbiota-associated products and pathways that are involved in this process.

Email: elizabeth.mann@manchester.ac.uk

Biography

I obtained a BSc in Genetics and an MSc in Molecular Medicine from University College London. I undertook my PhD in the laboratory of Professor Stella Knight at Imperial College London, focusing on human dendritic cell (DC) immunobiology, including tissue-specific specialization of human DC. I later trained as a postdoc at Johns Hopkins University in Baltimore in the laboratory of Dr Xuhang Li where I developed my expertise in murine models of IBD and molecular techniques, before joining the laboratory of Professor Simon Milling at the University of Glasgow. In this position, I investigated microbial interactions with intestinal immune cells to determine mechanisms by which broad-spectrum antibiotic use impacts on the intestinal immune system. Mid 2017 I moved to the University of Manchester as Wellcome Trust Sir Henry Dale Fellow and established an independent research group.

Biography

I obtained a BSc in Genetics and an MSc in Molecular Medicine from University College London. I undertook my PhD in the laboratory of Professor Stella Knight at Imperial College London, focusing on human dendritic cell (DC) immunobiology, including tissue-specific specialization of human DC. I later trained as a postdoc at Johns Hopkins University in Baltimore in the laboratory of Dr Xuhang Li where I developed my expertise in murine models of IBD and molecular techniques, before joining the laboratory of Professor Simon Milling at the University of Glasgow. In this position, I investigated microbial interactions with intestinal immune cells to determine mechanisms by which broad-spectrum antibiotic use impacts on the intestinal immune system. Mid 2017 I moved to the University of Manchester as Wellcome Trust Sir Henry Dale Fellow and established an independent research group.

Publications

  • Mann, E.R., Bernardo, D., English N.R., Landy, J., Al-Hassi, H.O., Peake, S.T.C., Man, R., Elliott, T., Spranger, H., Parian, A., Brant, S., Lazarev, M., Hart, A.L., Li, X. and Knight, S.C. (2016). Compartment-specific immunity in the human gut: properties and functions of dendritic cells in the colon versus the ileum. Gut. 65(2):256-70
  • Mann, E.R., Bernardo, D., Al-Hassi, H.O., Landy, J., Peake, S.T.C., Man, R., Han Lee, G., Yassin, N., Sarkar, S., Elliott, T., Thomas, L.V., Knight, S.C. and Hart, A.L. (2014). Human gut dendritic cells in ulcerative colitis drive aberrant, gut- specific T-cell responses characterised by increased IL-4 production and a loss of IL-22 and IFNγ. Inflammatory Bowel Diseases. 20(12): 2299-2307.
  • Mann, E.R. and Li, X. Intestinal antigen-presenting cells in mucosal immune homeostasis: crosstalk between dendritic cells, macrophages and B-cells (2014). World Journal of Gastroenterology. 7;20(29):9653-64.
  • Mann, E.R., Landy, J., Bernardo, D., Peake, S.T.C., Hart, A.L., Al-Hassi, H.O., and Knight, S.C. (2013). Review: Intestinal dendritic cells: their role in intestinal inflammation, manipulation by the gut microbiota and differences between mice and men. Immunology Letters. 150(1-2): 30-40.
  • Al-Hassi, H.O.*, Mann, E.R.* (equal contribution), Sanchez, B., English, N.R., Peake, S.T.C., Landy, J., Man, R., Urdaci, M., Hart, A.L., Fernandez-Salazar, L., Lee, G.H., Garrote, J.A., Arranz, E., Margolles A., Stagg, A.J., Knight, S.C. and Bernardo, D. (2013). Altered human gut dendritic cell properties in ulcerative colitis are reversed by Lactobacillus plantarum extracellular encrypted peptide STp. Molecular Nutrition and Food Research. 58(5):1132-43.
  • Mann, E.R., You, J., Bernardo, D., Al-Hassi, H.O., Peake, S.T.C., Thomas, L.V., Tee, C.T., Landy, J., Hart, A.L., Yaqoob, P. and Knight, S.C. (2013). Dysregulated circulating dendritic cell function in ulcerative colitis is partially restored by probiotic strain Lactobacillus casei Shirota. Mediators of Inflammation. 2013:573576.
  • Mann, E.R., McCarthy, N.E., Peake, S.T.C., Milestone, A.N., Al-Hassi, H.O., Bernardo, D., Tee, C.T., Landy, J., Pitcher, M.C., Cochrane, S.A., Hart, A.L., Stagg, A.J. and Knight, S.C. (2012). Skin- and gut-homing molecules on human circulating γδ T-cells and their dysregulation in inflammatory bowel disease. Clinical and Experimental Immunology. 170(2): 122-30.
  • Mann, E.R., Bernardo, D., Al-Hassi, H.O., English, N.R., Clark, S.K., McCarthy, N.E., Milestone, A.N., Cochrane, S.A., Hart, A.L., Stagg, A.J. and Knight, S.C. (2012). Human gut-specific homeostatic dendritic cells are generated from blood precursors by the gut microenvironment. Inflammatory Bowel Diseases. 18(7): 1275-1286.