The intracellular parasite Toxoplasma gondii is a category B priority pathogen that is a major food borne pathogen of humans and livestock, but very little is known about how the parasite is recognized and controlled by the immune system.
In Aim 1 we will examine the impact of innate immune signaling pathways on T. gondii infection using fibroblasts, dendritic cells, macrophage and mice containing defined genetic lesions. Particular emphasis will be placed on TRAIL-R and FADD (in collaboration with Project 2) and NK cells and the NK ligand NKG2D (in collaboration with Project 3).
In Aim 2 we will identify the major natural antigens recognized by CDS T cells during Toxoplasma infection. We hypothesize that the parasite antigens recognized by CDS T cells will vary depending on the stage of infection and the type of antigen presenting cells involved.
In Aim 3, we will examine the impact of innate immune responses and CD4 T cells on the response of CDS T cells. We will quantitate CDS T cell responses to particular antigens in mice lacking CD4 T cells or the innate immune pathways identified in Aim 1. We will also use 2-photon imaging to examine the dynamic aspects of immune responses in Aims 1 and 3.
|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|
|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 7:1716-1728|
|Young, Jennifer A; He, Tina H; Reizis, Boris et al. (2013) Commensal microbiota are required for systemic inflammation triggered by necrotic dendritic cells. Cell Rep 3:1932-44|
|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|
|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; 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|
|Dzhagalov, Ivan L; Melichar, Heather J; Ross, Jenny O et al. (2012) Two-photon imaging of the immune system. Curr Protoc Cytom Chapter 12:Unit12.26|
|Tam, Connie; LeDue, Jeffrey; Mun, James J et al. (2011) 3D quantitative imaging of unprocessed live tissue reveals epithelial defense against bacterial adhesion and subsequent traversal requires MyD88. PLoS One 6:e24008|
|Melichar, Heather J; Li, Ou; Herzmark, Paul et al. (2011) Quantifying subcellular distribution of fluorescent fusion proteins in cells migrating within tissues. Immunol Cell Biol 89:549-57|
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