Tajie H. Harris, Ph.D.
B.S., 2002, Bemidji State University
Ph.D., 2007, University of Wisconsin
2007-2013 Postdoctoral Research, University of
Harris Lab Website
Research in the Harris Laboratory
Toxoplasma gondii is an intracellular, protozoan parasite that infects approximately one-third of the world population. The parasite can be acquired congenitally or in adults, through the ingestion of contaminated food or water. Acute infection with T. gondii leads to systemic disease that is largely controlled by the cytokine, IFN-g. Despite this, the parasite persists in several tissues, including the brain and retina, where an ongoing T cell-mediated immune response is necessary to limit parasite replication. The vast majority of infections are asymptomatic, but suppression of T cell function can lead to severe toxoplasmic encephalitis and/or retinochoroiditis. While the importance of T cells in controlling T. gondii in the brain and eye has been demonstrated, research in the Harris laboratory aims to identify factors within immune-privileged tissues that influence local resistance to T. gondii.
Recently, Dr. Harris examined the CD8+ T cell response in the brain during chronic T. gondii infection using multi-photon (MP) microscopy and mathematical modeling. Statistical analysis revealed that T cell migration is described by a generalized Lévy walk (GLW), which is characterized by alternating runs and pauses. The GLW is similar to foraging strategies utilized by a variety of species from microzooplankton to monkeys. Subsequent mathematical modeling predicted that the chemokine, CXCL10, contributes to the immune response by decreasing the amount of time required for CD8+ T cells to reach infected target cells. To learn more about Dr. Harris’ recent research, click here.
These studies also raised several questions: Is the GLW behavior unique to CD8+ T cells? What additional chemokines affect T cell migration? How do CNS resident cells influence T cell migration? To address these questions, the Harris laboratory will use MP microscopy and other cutting-edge techniques to provide insight into the orchestration of local immune responses in the brain and retina.
The left-hand image depicts Foxp3+GFP-expressing cells (green) in contact with CD11c-YFP expressing cells (yellow) in the brains of live T. gondii-infected mice. Blood flow is shown in red and the skull bone in blue. The center image shows the tracks (lines) of regulatory T cells (green) in the brains of T. gondii infected mice. The images in the right panel depict parasite cysts within the retinas of infected mice. Cyst walls are show in red and individual parasites in green.
Harris, T.H., E. Banigan, D.A. Christian, C. Konradt, E.D. Tait Wojno, K. Norose, E.H. Wilson, B. John, W. Weninger, A.D. Luster, A. Liu, and C.A. Hunter. 2012. Generalized Lévy walks and the role of chemokines in migration of effector CD8+ T cells. Nature. 486: 545–548.
John, B., E.D. Tait Wojno, T.H. Harris, L.M. Randall, D. Manzoni De Almeida, D.A. Christian, B. Gregg, W. Weninger, D.A. Hammer, C.A. Hunter. 2011. Analysis of behavior and trafficking of dendritic cells within the brain during Toxoplasmic encephalitis. PLoS Pathog. 7: e1002246.
Sansing, L.H., T.H. Harris, S.E. Kasner, C.A. Hunter, K. Kariko. 2011. Neutrophil depletion diminishes monocyte infiltration and improves functional outcome after experimental intracerebral hemorrhage. Acta Neurochir Suppl . 111: 173-178.
K. Norose, A. Kikumura, A.D. Luster, C.A. Hunter, and T.H. Harris. 2011. CXCL10 is required to maintain T cell populations and control parasite replication during chronic ocular toxoplasmosis. Invest Ophthalmol Vis Sci. 52 (1): 389-398.
Harris, T.H., E.H. Wilson, E.D. Tait, M. Buckley, S. Shapira, J. Caamano, D. Artis, and C.A. Hunter. 2010. NF-kB1 contributes to T cell-mediated control of Toxoplasma gondii in the CNS. J. NeuroImmunol. 222: 19-28.
John B., T.H. Harris, E.D. Tait, E.H. Wilson, B. Gregg, L.G. Ng, P. Mrass, D.S. Roos, F. Dzierszinski, W. Weninger, C.A. Hunter. 2009. Dynamic Imaging of CD8+ T cells and dendritic cells during infection with Toxoplasma gondii. PLoS Pathog 5:e1000505
Wilson, E.H., T.H. Harris, P. Mrass, B. John, E.D. Tait, G.F. Wu, M. Pepper, E.J. Wherry, F. Dzierzinski, D. Roos, P.G. Haydon, T.M. Laufer, W. Weninger, and C.A. Hunter. 2009. Behavior of Parasite-Specific Effector CD8+ T Cells in the Brain and Visualization of a Kinesis-Associated System of Reticular Fibers. Immunity. 30(2): 300-311.
Tajie H. Harris
Center for Brain Immunology and Glia (BIG)
Department of Neuroscience
University of Virginia
409 Lane Road, MR-4 Room 6148
Charlottesville, VA 22908