The immunology and immunochemistry of two parasites responsible for disease in the United States are studied. Giardia lamblia is the most common disease-causing parasite in the United States responsible for an estimated 3 million cases a year The organism lives and multiples in the small intestines and by unknown means causes diarrhea, abdominal pain, nausea and vomiting. Symptoms are frequently intermittent and long lasting. An environmentally resistant cyst form is passed in the feces and because large numbers of cysts are excreted and only a few can cause infection, giardiasis is a very common problem in the developed regions as well as undeveloped areas of the world. Using a Giardia lamblia model infection in adult mice we previously showed that early in the infection T cells are essential to control the infection. This was surprising since it was thought that antibodies or B cells were essential to control infections. Chronic infections also occur in this model. Although mice are able to eliminate most Giardia organisms from the intestine, a small number persist. We are interested in determining if the suppression of infections during this chronic phase is the same as in the acute infection and the mechanisms involved. We are also studying if the few surviving organisms have a certain VSP on their surface and if the VSP changes over time. Earlier studies documented variability in infectivity of the same inoculum of Giardia for identical strains of mice obtained from different suppliers. We showed using SCID mice, a genetic mutation of mice that has no adaptive immunity, that the flora used by one supplier to colonize mice raised in that facility made these mice resistant to infection with Giardia. This is a potentially important observation because it may led to identification of certain bacterial strains in humans or animals that prevent infection with Giardia or other intestinal pathogens. The second group of parasites studied are microsporidia which are group of related protozoa that cause diarrhea and sometimes systemic infections in AIDS patients. Uncommonly they also cause diarrhea in normal persons. These organisms are also found in common farm animals and birds. Their importance in animals is being studied. Our studies have dealt with one of these parasites named Encephalitozoon intestinalis. We are interested in the identification and characterization of parasite proteins that are important for survival of the parasite in the host and host proteins that are called into play when the parasite invades the cell. In addition we have employed an immune mouse model of infection to define parasite antigens that the host recognizes and may be important for survival of the parasite or host. A number of proteins have been identified. However, the most important and perhaps useful is the identification of 2 spore wall proteins that are made by the parasite and join together to form the parasite wall. It is this wall that allows the parasite to survive outside the host and be infectious.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000161-23
Application #
6431517
Study Section
(LPD)
Project Start
Project End
Budget Start
Budget End
Support Year
23
Fiscal Year
2000
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Kulakova, Liudmila; Singer, Steven M; Conrad, John et al. (2006) Epigenetic mechanisms are involved in the control of Giardia lamblia antigenic variation. Mol Microbiol 61:1533-42
Hayman, J Russell; Southern, Timothy R; Nash, Theodore E (2005) Role of sulfated glycans in adherence of the microsporidian Encephalitozoon intestinalis to host cells in vitro. Infect Immun 73:841-8
Elmendorf, Heidi G; Rohrer, Sally C; Khoury, Rasha S et al. (2005) Examination of a novel head-stalk protein family in Giardia lamblia characterised by the pairing of ankyrin repeats and coiled-coil domains. Int J Parasitol 35:1001-11
Touz, Maria C; Kulakova, Liudmila; Nash, Theodore E (2004) Adaptor protein complex 1 mediates the transport of lysosomal proteins from a Golgi-like organelle to peripheral vacuoles in the primitive eukaryote Giardia lamblia. Mol Biol Cell 15:3053-60
Worgall, Tilla S; Davis-Hayman, Sara R; Magana, Marissa M et al. (2004) Sterol and fatty acid regulatory pathways in a Giardia lamblia-derived promoter: evidence for SREBP as an ancient transcription factor. J Lipid Res 45:981-8
Zhou, Ping; Li, Erqiu; Zhu, Nannan et al. (2003) Role of interleukin-6 in the control of acute and chronic Giardia lamblia infections in mice. Infect Immun 71:1566-8
Hinshaw, Jerald C; Suh, Dae-Yeon; Garnier, Philippe et al. (2003) Oxidosqualene cyclase inhibitors as antimicrobial agents. J Med Chem 46:4240-3
Touz, Maria C; Lujan, Hugo D; Hayes, Stanley F et al. (2003) Sorting of encystation-specific cysteine protease to lysosome-like peripheral vacuoles in Giardia lamblia requires a conserved tyrosine-based motif. J Biol Chem 278:6420-6
Davis-Hayman, Sara R; Hayman, J Russell; Nash, Theodore E (2003) Encystation-specific regulation of the cyst wall protein 2 gene in Giardia lamblia by multiple cis-acting elements. Int J Parasitol 33:1005-12
Touz, Maria C; Nores, Maria J; Slavin, Ileana et al. (2002) The activity of a developmentally regulated cysteine proteinase is required for cyst wall formation in the primitive eukaryote Giardia lamblia. J Biol Chem 277:8474-81

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