Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 6/24/2005
Publication Date: 8/29/2005
Citation: Tuo, W., Fetterer, R.H., Jenkins, M.C., Dubey, J.P. 2005. Neospora caninum cyclophilin: a interferon-gamma-inducing protein that may mediate the parasite-host interactions.. Meeting Abstract.
Technical Abstract: Interferon-gamma (IFN-gamma) response is required for the development of a host protective immunity when infected by intracellular parasites. Neosporosis, caused by the intracellular protozoan parasite Neospora caninum, is known to be fatal when there is a complete lack of IFN-gamma in the infected host. However, the mechanism to elicit IFN-gamma by the invading parasite is unclear. This study has identified a microbial protein in the N. caninum tachyzoite, N. caninum cyclophilin (NcCyP), as a major component of the parasite responsible for inducing IFN-gamma production by bovine peripheral blood mononuclear cells (PBMC) and antigen-specific CD4+ T cells. The NcCyP has high sequence homology (86%) with the T. gondii 18 kDa CyP and has a calculated molecular weight (Mr.) of 19.4 kDa. The NcCyP is a secretory protein with a predicted signal peptide of 17 amino acids. NcCyP has detectable isomerase activity and may not be N-glycosylated. NcCyP was detected in whole N. caninum tachyzoite lysate (NcAg) and culture supernatant of N. caninum tachyzoite. In N. caninum tachyzoite culture supernatant, three NcCyP bands of 19, 22, and 24 kDa were identified. NcAg induced high levels of IFN-gamma production by PBMC and CD4+ T cells in vitro. IFN-gamma-inducing effect of NcAg was blocked by cyclosporin A (CsA), a specific ligand for CyP, in a dose-dependent fashion. Furthermore, CsA abolished IFN-gamma production by PBMC from naïve cows and PBMC and CD4+ T cells from immune cows. These results indicate that the N. caninum tachyzoite naturally produces a IFN-gamma-inducing protein, NcCyP, which may in part mediate parasite survival as well as host protection.