1. Research Proposal: Neospora canimum causes abortion and congenital infection in multiple all hosts including non-human primates. Uniquely, vertical transmission is the primary means of dissemination of N. canimum. Once infected with N. canimum, hosts transmit the organism repeatedly during successive pregnancies indicating lack of development of long term immunity. Investigation of this disease offers a unique opportunity to study control of chronic protozoal disease in the pregnant host. A murine model of congenital transmission simulates natural disease. Mice experience a high rate of congenital infection and do not develop long term immunity. Limited information is known regarding immune of N. canimum, but preliminary data in the nonpregnant mouse demonstrates that a type 1 cytokine response controls parasite burden. This project tests the hypothesis that a reduction of maternal parasitemia by an acquired antigen specific type 1 response will prevent congenital transmission. Utilizing a murine model, the experiments will determine if concomitant antigen priming with avirulent low dose N. canimum and the cytokines IL-12 and IL-15 results in maternal immunity to congenital transmission. Should acquired immunity prevent congenital transmission, the hypothesis that protection against congenital protozoal transmission is mediated by MHC class I restricted cytotoxic T cells (CTL) will be tested. Information gained from these investigations will provide insight into control of congenitally transmitted protozoa. 2. Environment: Training occurs in an interactive environment with clinical and basic scientists. The sponsors have experience in protozoal immunology, molecular biology, and reproductive physiology and have successfully trained previous candidates. The program includes a structured seminar series for presentation of research results and interaction with scientists from other institutions.
| Long, M T; Baszler, T V (2000) Neutralization of maternal IL-4 modulates congenital protozoal transmission: comparison of innate versus acquired immune responses. J Immunol 164:4768-74 |
