Long term objectives are to reduce morbidity and mortality due to Toxoplasma infection through better understanding of immune responses to this organism and improved use of antimicrobial agents.
Specific aims are to study immune responses in a mouse model of Toxoplasma acquired by ingestion and in human congenital infections, and to develop optimal methods to interrupt congenital transmission of Toxoplasma and treat congenital toxoplasmosis. To further characterize immune response which protect mice that ingest Toxoplasma, inbred strains of mice will be used to evaluate the role of cytotoxic cells, H2 haplotype, Ity/Lsh/Bcg and H13 loci in protection against lethal toxoplasmosis. As a correlate of these studies, assays will be performed to determine whether there are Toxoplasma antigens on the surface of infected or antigen pulsed mouse macrophages that render them targets for lysis. Mechanisms causing depressed T cell function and lack of splenic lymphocyte blastogenesis to Toxoplasma antigens at a time when peritoneal macrophages are activated will be evaluated with the mouse model. Influence of Toxoplasma antigen specific cloned helper T lymphocytes, high titers of specific anti-Toxoplasma antibody, activated macrophages or an attenuated mutant Toxoplasma on acquisition of peroral or congenital Toxoplasma will be determined with the mouse model. Study of immune responses in human congenital infections will be by evaluation of lymphocyte blastogenic responses to Toxoplasma antigens, measurement of T cell subsets, and lymphocyte and monocyte function. To develop optimal strategies to manage human congenital Toxoplasma infection a serologic screening program to diagnose Toxoplasma infection acquired during pregnancy will be evaluated and congenitally infected infants identified in this program (and through collaborative arrangements) will be studies prospectively to determine optimal treatment regimens and establish pharmacokinetics of the antimicrobial agents used.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI016945-04A2
Application #
3126922
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1980-07-01
Project End
1987-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Michael Reese Hosp & Medical Center (Chicago)
Department
Type
DUNS #
City
Chicago
State
IL
Country
United States
Zip Code
60616
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Estes, R; Vogel, N; Mack, D et al. (1998) Paclitaxel arrests growth of intracellular Toxoplasma gondii. Antimicrob Agents Chemother 42:2036-40
Mets, M B; Holfels, E; Boyer, K M et al. (1997) Eye manifestations of congenital toxoplasmosis. Am J Ophthalmol 123:1-16

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