Abstract

This project represents an experimental model system for the study of human and animal disease caused by the African trypanosomes. A continuation of studies which examine the immunobiological relationship between host and parasite in Trypanosoma brucei rhodesiense infected inbred mice is proposed.
The specific aims of the project are (1) to define at the molecule and cellular levels the nature of host immune responses to defined epitopes of trypanosome variant-specific and invariant antigens; (2) to examine at the molecular and cellar levels the means by which infected hosts regulate parasite-specific immune responses; (3) to determine how non-MHC-associated genetic differences influence the overall resistance status of the infected host strain; and (4) to define the molecular and genetic bases of virulence expression in trypanosomes which alter host immunity and resistance characteristics. Contemporary immunology and molecular biology form the conceptual and technique framework of this project.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI022441-08
Application #
3133500
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1985-01-01
Project End
1993-03-31
Budget Start
1992-01-01
Budget End
1993-03-31
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
University of Wisconsin Madison
Department
Type
Schools of Earth Sciences/Natur
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715

  Publications

Inverso, Jill A; Uphoff, Timothy S; Johnson, Scott C et al. (2010) Biological variation among african trypanosomes: I. Clonal expression of virulence is not linked to the variant surface glycoprotein or the variant surface glycoprotein gene telomeric expression site. DNA Cell Biol 29:215-27
Dagenais, Taylor R; Freeman, Bailey E; Demick, Karen P et al. (2009) Processing and presentation of variant surface glycoprotein molecules to T cells in African trypanosomiasis. J Immunol 183:3344-55
Dagenais, Taylor R; Demick, Karen P; Bangs, James D et al. (2009) T-cell responses to the trypanosome variant surface glycoprotein are not limited to hypervariable subregions. Infect Immun 77:141-51
Lopez, Rebecca; Demick, Karen P; Mansfield, John M et al. (2008) Type I IFNs play a role in early resistance, but subsequent susceptibility, to the African trypanosomes. J Immunol 181:4908-17
Mansfield, J M; Paulnock, D M (2008) Genetic manipulation of African trypanosomes as a tool to dissect the immunobiology of infection. Parasite Immunol 30:245-53
Harris, Tajie H; Mansfield, John M; Paulnock, Donna M (2007) CpG oligodeoxynucleotide treatment enhances innate resistance and acquired immunity to African trypanosomes. Infect Immun 75:2366-73
Harris, Tajie H; Cooney, Nicole M; Mansfield, John M et al. (2006) Signal transduction, gene transcription, and cytokine production triggered in macrophages by exposure to trypanosome DNA. Infect Immun 74:4530-7
Curran, Colleen S; Demick, Karen P; Mansfield, John M (2006) Lactoferrin activates macrophages via TLR4-dependent and -independent signaling pathways. Cell Immunol 242:23-30
Dubois, Melissa E; Demick, Karen P; Mansfield, John M (2005) Trypanosomes expressing a mosaic variant surface glycoprotein coat escape early detection by the immune system. Infect Immun 73:2690-7
Coller, Susan P; Mansfield, John M; Paulnock, Donna M (2003) Glycosylinositolphosphate soluble variant surface glycoprotein inhibits IFN-gamma-induced nitric oxide production via reduction in STAT1 phosphorylation in African trypanosomiasis. J Immunol 171:1466-72

Showing the most recent 10 out of 27 publications