Studies will be performed to provide a better understanding of the biology and immunology of Toxoplasma gondii, the epidemiology, diagnosis and treatment of acute and chronic congenital and acquired toxoplasmosis, and the unique role of Toxoplasma in infection in the immunologically compromised patient. Purified preparations of antigens of the three stages of T. gondii will be isolated and characterized and used to study the humoral and cell-mediated immune response. Monoclonal antibodies will be formed against each of the three stages to use in studies on resistance and for detection and purification of antigens. The antigens and antibodies will be used to improve, develop, and evaluat methods for serologic diagnosis of all stages of the infection in animals and humans. We will study the nature of immune aggregates containing Toxoplasma antigens which are formed in humans with the infection and determine their role in the pathogenesis and diagnosis of the disease. The clinical manifestations, immune response, and methods of diagnosis in the immunocompromised patient will be studied as will genetic predisposition to various forms of acquired toxoplasmosis in normal humans. The immune response to Toxoplasma during pregnancy and the relationship of Toxoplasma to spontaneous abortion will be explored. The role of cell-mediated immunity and particularly the role of the macrophage in resistance to T. gondii will be studied and the biochemical mechanisms of inhibition and killing of the intracellular organism will be examined. An attempt will be made to define the relative roles of cell-mediated and humoral immunity in resistance to the organism and to define the mechanisms underlying the immunosuppression caused by Toxoplasma in laboratory animals and humans. Long-term follow-up of adverse sequelae in children born with asymptomatic congenital Toxoplasma infection will be performed and a series of studies will be executed to define newer therapeutic means for treatment of the congenital and acquired forms of toxoplasmosis. Because of their cross reactivity in serologic tests and in vivo, we will compare and contrast the antigen relationship between Toxoplasma and Hammondia and examine the cross resistance which exists in vivo against these organisms.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI004717-25
Application #
3124199
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1977-04-01
Project End
1987-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
25
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Palo Alto Medical Foundation Research Institute
Department
Type
DUNS #
622276137
City
Palo Alto
State
CA
Country
United States
Zip Code
94301
Montoya, Jose G; Huffman, Heather B; Remington, J S (2004) Evaluation of the immunoglobulin G avidity test for diagnosis of toxoplasmic lymphadenopathy. J Clin Microbiol 42:4627-31
Remington, Jack S; Thulliez, Philippe; Montoya, Jose G (2004) Recent developments for diagnosis of toxoplasmosis. J Clin Microbiol 42:941-5
Araujo, F; Slifer, T; Li, S et al. (2004) Gemifloxacin inhibits cytokine secretion by lipopolysaccharide stimulated human monocytes at the post-transcriptional level. Clin Microbiol Infect 10:213-9
Wang, Xisheng; Kang, Hoil; Kikuchi, Takane et al. (2004) Gamma interferon production, but not perforin-mediated cytolytic activity, of T cells is required for prevention of toxoplasmic encephalitis in BALB/c mice genetically resistant to the disease. Infect Immun 72:4432-8
Araujo, Fausto G; Slifer, Teri (2003) Different strains of Toxoplasma gondii induce different cytokine responses in CBA/Ca mice. Infect Immun 71:4171-4
Kang, Hoil; Liesenfeld, Oliver; Remington, Jack S et al. (2003) TCR V beta 8+ T cells prevent development of toxoplasmic encephalitis in BALB/c mice genetically resistant to the disease. J Immunol 170:4254-9
Yardley, Vanessa; Khan, Anis A; Martin, Michael B et al. (2002) In vivo activities of farnesyl pyrophosphate synthase inhibitors against Leishmania donovani and Toxoplasma gondii. Antimicrob Agents Chemother 46:929-31
Parmley, Stephen; Slifer, Teri; Araujo, Fausto (2002) Protective effects of immunization with a recombinant cyst antigen in mouse models of infection with Toxoplasma gondii tissue cysts. J Infect Dis 185 Suppl 1:S90-5
Suzuki, Yasuhiro (2002) Host resistance in the brain against Toxoplasma gondii. J Infect Dis 185 Suppl 1:S58-65
Montoya, Jose G; Liesenfeld, Oliver; Kinney, Sandra et al. (2002) VIDAS test for avidity of Toxoplasma-specific immunoglobulin G for confirmatory testing of pregnant women. J Clin Microbiol 40:2504-8

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