The long-term goal of the proposed research is to analyze factors which influence the ability of neonates to resist infectious agents and to be vaccinated successfully against them. Infection with the protozoan parasite Toxoplasma gondii will be used as a model system. Neonatal mice possess a mechanism, dependent on Thy-1+ CD4-CD8- cells and IFN-gamma, that allows a majority of them to survive the acute phase of a primary infection with the protozoan parasite T. gondii. Mice that survive neonatal T. gondii infection exhibit resistance to rechallenge with highly virulent parasites as adults, but the level of protection is inferior to that of adult-immunized controls. Using T. gondii infection as a model system we will (1) analyze the cells and cytokines produced by neonates to learn more about their protective capabilities, (2) analyze how cells and positive and negative regulatory cytokines induced during a primary acute infection in neonatal mice affect the generation of acquired resistance expressed in adults, and (3) analyze acquired immunity in mice vaccinated as neonates and adults to determine the basis for the lesser resistance expressed by neonatally immunized mice.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI037090-01
Application #
2073691
Study Section
Special Emphasis Panel (SRC (84))
Project Start
1994-09-30
Project End
1998-06-30
Budget Start
1994-09-30
Budget End
1995-06-30
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Trudeau Institute, Inc.
Department
Type
DUNS #
City
Saranac Lake
State
NY
Country
United States
Zip Code
12983
Sayles, P C; Gibson, G W; Johnson, L L (2000) B cells are essential for vaccination-induced resistance to virulent Toxoplasma gondii. Infect Immun 68:1026-33
Aguirre, K M; Garvy, B A; Johnson, L L (1997) Acquired resistance to Cryptococcus neoformans in adult mice vaccinated as newborns. Infect Immun 65:1688-94
Sayles, P C; Johnson, L L (1996) Intact immune defenses are required for mice to resist the ts-4 vaccine strain of Toxoplasma gondii. Infect Immun 64:3088-92
Johnson, L L; Gibson, G W; Sayles, P C (1996) CR3-dependent resistance to acute Toxoplasma gondii infection in mice. Infect Immun 64:1998-2003
Sayles, P C; Johnson, L L (1996) Exacerbation of toxoplasmosis in neutrophil-depleted mice. Nat Immun 15:249-58
Aguirre, K M; Sayles, P C; Gibson, G W et al. (1996) Resistance to Cryptococcus neoformans is associated with an inflammatory response to Toxoplasma gondii in the central nervous system of mice. Infect Immun 64:77-82
Johnson, L L; Gibson, G W; Sayles, P C (1995) Toxoplasma gondii: effect of sublethal irradiation on host resistance in mice. Exp Parasitol 81:172-81
Johnson, L L; Sayles, P C (1995) Strong cytolytic activity of natural killer cells is neither necessary nor sufficient for preimmune resistance to Toxoplasma gondii infection. Nat Immun 14:209-15