Dr Kevin Couper
Kevin Couper – Research summary
Malaria remains one of the most severe parasitic infections of humans in the world. It is estimated that over 250 million people become infected with malaria each year, resulting in over 1.2 million deaths, mainly of young children in Sub Saharan Africa, each year. Although the Plasmodium protozoan parasite was first shown to be the causative agent of malaria over 130 years ago, we still have a very poor understanding of why some individuals are susceptible to malaria infection and why others are resistant. This is in large part due to our lack of knowledge of the pathogenesis of the most severe complications of malaria infection, such as cerebral malaria and lung damage. My group use murine models of malaria and employ a variety of novel and established techniques to investigate parasitological and immunological processes that cause severe malarial disease. Delineating the pathways that cause severe malaria should directly facilitate the development of adjunct treatments that can be used in combination with anti-malarial drugs to ameliorate malarial disease.
We also use murine models of malaria to dissect how effector and regulatory immune responses develop during malaria infection. Although generation of effector T cell responses is essential for the control and clearance of the malaria parasite during infection, we now know that failure to regulate the pro-inflammatory cascades can lead to severe tissue damage and pathology. By dissociating the signals responsible for induction of pro-inflammatory and regulatory immune responses during malaria infection we should be able to manipulate the immune response therapeutically to optimise the control and resolution of infection.
Themes: Infectious disease | T–cells, Tregs and autoimmunity | Dissecting the cellular cytokine network | CNS inflammation
Kevin Couper – People
Dr Ana Villegas Mendez
Kevin Couper – People
Dr Ana Villegas Mendez
James Brewer, University of Glasgow, UK
Chris Janse and Shahid Khan, LUMC, Leiden, Netherlands
Chris Hunter, U Penn, Philadelphia, USA
Brian de Souza, LSHTM, London, UK
Kevin is a MRC Career Development Fellow in the Immunology Research Group in the Faculty of Life Sciences
Kevin graduated with a BSc in Biochemistry and Immunology at the University of Strathclyde, Glasgow in 1999. Kevin then completed a PhD at the University of Strathclyde in 2003 with Professor Jim Alexander, studying the immune response to the related protozoan parasites Toxoplasma gondii and Plasmodium chabaudi AS. Kevin then completed two post-doctoral positions, first at the Trudeau Institute, USA, and then at the London School of Hygiene, London, studying how protective and regulatory immune responses develop and function during Toxoplasma gondii and malaria infections. Kevin became a lecturer at LSHTM in 2008 and was awarded a MRC Career Development Award in 2009 to define the parasitological and immunological basis of cerebral pathology during murine experimental cerebral. Kevin moved to The University of Manchester in 2012 to study the immune response to malaria infection.
- Villegas-Mendez, A., J. B. de Souza, L. Murungi, J. C. R. Hafalla, T. N. Shaw, R. Greig, E. M. Riley and K. N. Couper. 2011. Heterogeneous and tissue specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection. J. Immunol 187:2885-97
- Findlay, E. G., R. Greig, J. S. Stumhofer, J. C. Hafalla, J. B. de Souza, C. J. Saris, C. A. Hunter, E. M. Riley, and K. N. Couper. 2010. Essential role for IL-27 receptor signaling in prevention of Th1-mediated immunopathology during malaria infection. J Immunol 185:2482-2492.
- Couper, K. N., T. Barnes, J. C. Hafalla, V. Combes, B. Ryffel, T. Secher, G. E. Grau, E. M. Riley, and J. B. de Souza. 2010. Parasite-derived plasma microparticles contribute significantly to malaria infection-induced inflammation through potent macrophage stimulation. PLoS Pathog 6:e1000744.
- Couper, K. N., P. A. Lanthier, G. Perona-Wright, L. W. Kummer, W. Chen, S. T. Smiley, M. Mohrs, and L. L. Johnson. 2009. Anti-CD25 antibody-mediated depletion of effector T cell populations enhances susceptibility of mice to acute but not chronic Toxoplasma gondii infection. J Immunol 182:3985-3994.
- Couper, K. N., D. G. Blount, M. S. Wilson, J. C. Hafalla, Y. Belkaid, M. Kamanaka, R. A. Flavell, J. B. de Souza, and E. M. Riley. 2008. IL-10 from CD4CD25Foxp3CD127 adaptive regulatory T cells modulates parasite clearance and pathology during malaria infection. PLoS Pathog 4:e1000004.
- Couper, K. N., D. G. Blount, and E. M. Riley. 2008. IL-10: the master regulator of immunity to infection. J Immunol 180:5771-5777.