Toxoplasma gondii is an important parasitic infection causing much morbidity and mortality in patients with primary or acquired immunodeficiencies. Because production of IFNg is crucial in both innate and adaptive immunity to toxoplasmosis, understanding the molecular mechanisms involved in the induction of this cytokine will be paramount to developing novel treatment strategies. The transcription factor NF-kB has been implicated in the production of IFNg by both NK and T cells; principal mediators of innate and adaptive immunity to toxoplasmosis respectively. Using retroviral gene transfection to selectively inhibit NF-kB signaling, it will be possible to assess the role of this transcription factor in the production of IFNg by NK cells in vitro. In addition, by reconstituting sublethally irradiated RAG -/- mice with these virally transfected cells, the importance of NF-kB signaling in innate immunity to toxoplasmosis can be determined in vivo. Furthermore, by employing a transgenic mouse model in which NF-kB signaling is inhibited in T cells, the role of NF-kB activation in T cell mediated resistance to T. gondii infection can be determined.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AI010662-02
Application #
6453532
Study Section
Special Emphasis Panel (ZRG1-MDCN-7 (02))
Program Officer
Hernandez, Milton J
Project Start
2001-09-30
Project End
Budget Start
2001-09-30
Budget End
2002-09-29
Support Year
2
Fiscal Year
2001
Total Cost
$34,392
Indirect Cost
Name
University of Pennsylvania
Department
Pathology
Type
Schools of Veterinary Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104