Toxoplasma gondii is an intracellular protozoan parasite that is the causative agent of Toxoplasmosis. Toxoplasma infection in mice provides an excellent experimental model for understanding food borne infections and chronic infections of the brain. The overall goal of this project is to gain a deeper understanding of how the mammalian immune system responds to chronic Toxoplasma infection by tracking parasites and immune cells in the brain. Specifically, we propose to examine how T cell interactions with parasites and invaded host cells changes during progressing versus controlled chronic infection (Aim 1), to investigate the key features that distinguish a protective CD8 T cell response from a non-protective one (Aim 2), and to investigate the role of regulatory T cells in modulating T cell effectors responses (Aim 3).
Toxoplasma gondii is a parasite that causes birth defects or brain infection in immune compromised adults. We are using a mouse infection model and advanced microscopy methods to gain a better understanding of how the immune system protects against the parasite and how the parasite attempts to evade the immune system. Because Toxoplasma establishes life-long infection of the brain, these studies have relevance for the development of therapeutic strategies to treat infections of the brain and chronic infections.
|Chu, H Hamlet; Chan, Shiao-Wei; Gosling, John Paul et al. (2016) Continuous Effector CD8(+) T Cell Production in a Controlled Persistent Infection Is Sustained by a Proliferative Intermediate Population. Immunity 45:159-71|
|Ueno, Norikiyo; Lodoen, Melissa B; Hickey, Graeme L et al. (2015) Toxoplasma gondii-infected natural killer cells display a hypermotility phenotype in vivo. Immunol Cell Biol 93:508-13|
|Han, Seong-Ji; Melichar, Heather J; Coombes, Janine L et al. (2014) Internalization and TLR-dependent type I interferon production by monocytes in response to Toxoplasma gondii. Immunol Cell Biol 92:872-81|
|Grover, Harshita Satija; Chu, H Hamlet; Kelly, Felice D et al. (2014) Impact of regulated secretion on antiparasitic CD8 T cell responses. Cell Rep 7:1716-28|
|Coombes, Janine L; Charsar, Brittany A; Han, Seong-Ji et al. (2013) Motile invaded neutrophils in the small intestine of Toxoplasma gondii-infected mice reveal a potential mechanism for parasite spread. Proc Natl Acad Sci U S A 110:E1913-22|
|Ingram, Wendy Marie; Goodrich, Leeanne M; Robey, Ellen A et al. (2013) Mice infected with low-virulence strains of Toxoplasma gondii lose their innate aversion to cat urine, even after extensive parasite clearance. PLoS One 8:e75246|
|Coombes, Janine L; Han, Seong-Ji; van Rooijen, Nico et al. (2012) Infection-induced regulation of natural killer cells by macrophages and collagen at the lymph node subcapsular sinus. Cell Rep 2:124-35|
|Grover, Harshita Satija; Blanchard, Nicolas; Gonzalez, Federico et al. (2012) The Toxoplasma gondii peptide AS15 elicits CD4 T cells that can control parasite burden. Infect Immun 80:3279-88|
|Coombes, Janine L; Robey, Ellen A (2010) Dynamic imaging of host-pathogen interactions in vivo. Nat Rev Immunol 10:353-64|