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Immunochemistry of Parasitic Diseases

Investigators
Nash, Theodore
Institutions
DHHS/NIH - National Institute of Allergy and Infectious Diseases
Start date
2000
End date
2000
Objective
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 lead 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.

Funding Source
Nat'l. Inst. of Allergy and Infectious Diseases
Project number
1Z01AI000161-23
Categories
Bacterial Pathogens
Parasites
Giardia