In the US, Toxoplasma Gondi is the second leading cause of food borne mortality and more than 60 million people are persistently infected with this organism and this infection is a concern in many patients with primary or acquired defects in T cell mediated immunity. Due to the ease of transmission and its ability to cause severe disease, T. Gondi is classified as a Class B Biodefense pathogen. The initial interaction between Toxoplasma and host macrophages and dendritic cells is key in determining the outcome of this infection and this parasite can inject proteins into uninfected host cells that are thought to antagonize their ability to control infection. Using novel transgenic parasites combined wth unique mouse strains and advanced imaging technologies we are now able to identify these injected but uninfected populations and propose experiments to determine whether these events affect the innate host response or the development of the adaptive response required for long term control of T. gondii.

Public Health Relevance

Toxoplasma is a common opportunistic infection in patients with defects in T cell function and can cause significant disease in immune competent individuals. This parasite has a variety of strategies to avoid the immune system. The overall goal of this proposal is to understand how the pathogen evades the immune system with the aim of making better vaccines and treatments.

Agency
National Institute of Health (NIH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI104998-02
Application #
8656666
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Wali, Tonu M
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Pathology
Type
Schools of Veterinary Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Christian, David A; Koshy, Anita A; Reuter, Morgan A et al. (2014) Use of transgenic parasites and host reporters to dissect events that promote interleukin-12 production during toxoplasmosis. Infect Immun 82:4056-67
Glatman Zaretsky, Arielle; Engiles, Julie B; Hunter, Christopher A (2014) Infection-induced changes in hematopoiesis. J Immunol 192:27-33
Beiting, Daniel P; Peixoto, Lucia; Akopyants, Natalia S et al. (2014) Differential induction of TLR3-dependent innate immune signaling by closely related parasite species. PLoS One 9:e88398
Dupont, Christopher D; Christian, David A; Selleck, Elizabeth M et al. (2014) Parasite fate and involvement of infected cells in the induction of CD4+ and CD8+ T cell responses to Toxoplasma gondii. PLoS Pathog 10:e1004047