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 congenitally and in human congenital infections, and to develop optimal methods to interrupt congenital transmission of Toxoplasma and treat congenital toxoplasmosis. To further characterize immune responses which protect mice that ingest Toxoplasma, the antigens recognized by and protective effect of Toxoplasma specific intestinal antibodies against peroral and congenital infection will be characterized. Attenuated tachyzoites, bradyzoites and antigens of T. gondii alone, or antigens conjugated to cholera-toxin subunit B or synthesized by a cloned portion of the T. gondii genome recombined into a mouse Salmonella plasmid will be used to attempt to produce specific intestinal IgA. Monoclonal and polyclonal antibodies will be tested for their ability to block entry into or replication within enterocytes and to interrupt peroral and/or ongenital acquisition. Antigens will be studied to determine which epitopes bind to enterocytes. Studies will also be continued to characterize the gene(s) and gene product(s) that result(s) in differences in early survival of and numbers of latent brain cysts in recombinant inbred AXB/BXA mice on the A/J (resistant) and C57B1/6J (susceptible) backgrounds. Study of immune responses in human congenital infections will be continued by evaluation of lymphocyte blastogenic responses to Toxoplasma antigens, measurement of T cell subsets, and lymphocyte functions. To development 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 studied prospectively to determine optimal treatment regimens and establish pharmacokinetics of the antimicrobial agents used.
|Jamieson, S E; Peixoto-Rangel, A L; Hargrave, A C et al. (2010) Evidence for associations between the purinergic receptor P2X(7) (P2RX7) and toxoplasmosis. Genes Immun 11:374-83|
|Arun, Veena; Noble, A Gwendolyn; Latkany, Paul et al. (2007) Cataracts in congenital toxoplasmosis. J AAPOS 11:551-4|
|Johnson, Jennifer J; Roberts, Craig W; Pope, Constance et al. (2002) In vitro correlates of Ld-restricted resistance to toxoplasmic encephalitis and their critical dependence on parasite strain. J Immunol 169:966-73|
|Johnson, Jennifer; Suzuki, Yasuhiro; Mack, Douglas et al. (2002) Genetic analysis of influences on survival following Toxoplasma gondii infection. Int J Parasitol 32:179-85|
|Roberts, F; Roberts, C W; Ferguson, D J et al. (2000) Inhibition of nitric oxide production exacerbates chronic ocular toxoplasmosis. Parasite Immunol 22:5-Jan|
|Roberts, F; McLeod, R (1999) Pathogenesis of toxoplasmic retinochoroiditis. Parasitol Today 15:51-7|
|Mack, D G; Johnson, J J; Roberts, F et al. (1999) HLA-class II genes modify outcome of Toxoplasma gondii infection. Int J Parasitol 29:1351-8|
|Zuther, E; Johnson, J J; Haselkorn, R et al. (1999) Growth of Toxoplasma gondii is inhibited by aryloxyphenoxypropionate herbicides targeting acetyl-CoA carboxylase. Proc Natl Acad Sci U S A 96:13387-92|
|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|
Showing the most recent 10 out of 37 publications