Abstract

The immunobiological relationship between host and parasite in African trypanosomiasis is the focus of this proposal. Recent evidence suggests that macrophage activation is associated with regulation of T cell responses as well as development of host resistance during infection. Accordingly we hypothesize that events controlling macrophage activation influence the course of infection. Thus, the cellular and molecular mechanisms that affect macrophage activation and parasite antigen specific T cell stimulation in infected animals, and the immunological consequences of such events, comprise the specific aims of the project. An experimental model system of the human disease will be studied in which inbred strains of mice differing in immune responsiveness and susceptibility are infected with well characterized Trypanosoma brucei rhodesiense clones that express different antigenic and biological traits.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI022441-09
Application #
3133494
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1985-01-01
Project End
1998-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
9
Fiscal Year
1993
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
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
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
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