Abstract

The overall objective of this proposal is to examine the immunobiological relationship between host and parasite in experimental African trypanosomiasis. The role of trypanosome antigen-specific B and T cell responses, and the role of the macrophage, in providing protection and controlling parasitemia are being assessed. The role of the parasite-specific immune response in inducing pathology is also being determined. Finally, the ability of the trypanosome to modulate host immune responses to the trypanosome surface antigens is being measured, and efforts are being made to manipulate such parasite-specific responses so as to provide more protection and less pathology. Thus, the proposed research will carefully dissect numerous aspects of the immunology in the host-parasite relationship in experimental African trypanosomiasis, and addresses questions of fundamental importance in medical and veterinary tropical disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI022441-03
Application #
3133496
Study Section
(SSS)
Project Start
1985-01-01
Project End
1987-12-31
Budget Start
1987-01-01
Budget End
1987-12-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Wisconsin Madison
Department
Type
Earth Sciences/Resources
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