This project comprises the cellular/molecular analyses of T helper subset functions and the generation of inflammatory, regulatory signals that participate in the evolution, florid state and involution of the S mansoni egg-induced granulomatous inflammation. Our long range objective is to elucidate the mechanisms of granuloma formation and design immunologic interventions to ameliorate granulomatous pathology in schistosomiasis mansoni. The research objectives are divided into three interrelated areas: 1. Th1, Th2 paradigm and the polarization of granuloma formation. Immune interventions by recombinant cytokines, anti-cytokine abs are done to polarize in infected mice the mixed T subset response into Th1 or Th2 mode. Stat-deficient and Th1, Th2 cell injected mice are used to establish Th1 or Th2 type granuloma models confirmed by cytokine mRNA expression (RT-PCR) or production profile. The roles of Th1, and NK cells in granuloma induction, suppression, subset cross regulation, along with chemokine participation, are examined. 2. Schistosome eggs-mediated endothelial cell activation. Egg antigen(s) induced endothelial cell activation expressed by adhesion molecule display, cytokine secretion, proliferation and angiogenesis will be examined in vitro. 3. Role of adhesion molecules and extracellular matrix in granuloma evolution, fibrosis and involution. The role of membrane adhesion molecules in leukocyte interactions, granuloma evolution and extracellular matrix deposition is elucidated in antibody treated or adhesion molecule deficient mice. The influence of Th1, Th2 cells on matrix formation fibrosis and the role of matrix- derived signals on T cell activation or apoptosis are investigated.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI012913-22A1
Application #
2460928
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1979-06-01
Project End
2002-12-31
Budget Start
1998-01-01
Budget End
1998-12-31
Support Year
22
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Wayne State University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202