Harris, Tajie H.
- BS, Biology, Bemidji State University
- PhD, Microbiology, University of Wisconsin-Madison
- Postdoc, Immunoparasitology, University of Pennsylvania
Immune response to infectious disease in the CNS
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 Lečvy 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.
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.