Schistosomiasis, the parasitic disease caused by blood flukes of the genus Schistosoma, causes potentially serious liver, intestine and urinary system pathology in approximately 200 million people worldwide, resulting in significant morbidity and mortality. In addition to constituting a major public health concern for people living in endemic areas in South America, Africa and Asia, schistosomiasis is also a significant concern for U.S. service personnel, Peace Corps workers and civilians visiting regions where blood flukes are prevalent. High re-infection rates following treatment and the potential for development of resistance to the few effective chemotherapeutics for schistosomiasis has prompted efforts to develop vaccines that prevent infection and/or disease. While an effective vaccine has not yet been developed, evidence from field and laboratory studies indicate that CD4+ T cell responses will be critical components of the response induced by an effective vaccine. However, our studies using a murine model of schistosome infection have demonstrated that, paradoxically, schistosomes also require signals from host CD4+ T cells to complete their development normally, suggesting that blocking interactions between parasite and host T cells might provide a novel approach to interfering with parasite development. The long-term objective of our studies is to contribute to the development of new immunotherapies aimed at preventing schistosome development in the definitive human host, thus simultaneously preventing the pathology associated with schistosome infection and blocking parasite transmission. The overall aim of this study is to further our understanding of the role CD4+ T cells play in facilitating the development and reproduction of Schistosoma blood flukes.
The specific aims of this study are (1) to determine whether the presence of CD4* T cells alone is sufficient to facilitate parasite development, (2) to determine whether CD4+ T cell responses to schistosome antigens are important in influencing the outcome of schistosome development, and (3) determine the role of the CD4+ T cell cytokine interleukin-2 (IL-2) in affecting the outcome of schistosome development.
Specific aim 1 will be accomplished by examining schistosome infections in a transgenic mouse model where none of the animal's CD4+ T cells are able to respond to schistosome antigens because of their restricted specificity for an unrelated antigen.
Specific aim 2 will be accomplished by selectively reconstituting immunodeficient mice with CD4+ T cells that can or cannot respond to schistosome antigens prior to infection and then examining the effect of activation with the appropriate antigen on parasite development.
Specific aim 3 will be addressed by examining schistosome infection in IL-2-deficient mice.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Pathogenic Eukaryotes Study Section (PTHE)
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Wali, Tonu M
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Henry M. Jackson Fdn for the Adv Mil/Med
United States
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Riner, Diana K; Ferragine, Christine E; Maynard, Sean K et al. (2013) Regulation of innate responses during pre-patent schistosome infection provides an immune environment permissive for parasite development. PLoS Pathog 9:e1003708
Ferragine, Christine E; Walls, Colleen D; Davies, Stephen J (2013) Modulation of innate antigen-presenting cell function by pre-patent schistosome infection. PLoS Negl Trop Dis 7:e2136
Swierczewski, Brett E; Davies, Stephen J (2010) Conservation of protein kinase a catalytic subunit sequences in the schistosome pathogens of humans. Exp Parasitol 125:156-60
Swierczewski, Brett E; Davies, Stephen J (2010) Developmental regulation of protein kinase A expression and activity in Schistosoma mansoni. Int J Parasitol 40:929-35
de Oliveira Fraga, Lucia Alves; Torrero, Marina N; Tocheva, Anna S et al. (2010) Induction of type 2 responses by schistosome worms during prepatent infection. J Infect Dis 201:464-72
Lamb, Erika W; Walls, Colleen D; Pesce, John T et al. (2010) Blood fluke exploitation of non-cognate CD4+ T cell help to facilitate parasite development. PLoS Pathog 6:e1000892
de Oliveira Fraga, Lucia A; Lamb, Erika W; Moreno, Elizabeth C et al. (2010) Rapid induction of IgE responses to a worm cysteine protease during murine pre-patent schistosome infection. BMC Immunol 11:56
Swierczewski, Brett E; Davies, Stephen J (2009) A schistosome cAMP-dependent protein kinase catalytic subunit is essential for parasite viability. PLoS Negl Trop Dis 3:e505
Lamb, Erika W; Crow, Emily T; Lim, K C et al. (2007) Conservation of CD4+ T cell-dependent developmental mechanisms in the blood fluke pathogens of humans. Int J Parasitol 37:405-15
Blank, Rebecca B; Lamb, Erika W; Tocheva, Anna S et al. (2006) The common gamma chain cytokines interleukin (IL)-2 and IL-7 indirectly modulate blood fluke development via effects on CD4+ T cells. J Infect Dis 194:1609-16