Murine salmonellosis is used as the experimental model to resolve the current controversy of whether pathogenic salmonellae do survive and multiply within host phagocytes. Electron microscopic studies on the peritoneal exudate cells and on the liver of mice infected with Salmonella typhimurium have now shown that salmonellae are killed within inflammatory polymorphs and macrophages and multiply in the extracellular space and within hepatocytes. Continuation of this project in the next three years will be directed (a) to certify that the bacteria seen in the tissues are in fact salmonellae and that intracytoplasmic debris seen in the phagocytes does contain salmonella antigens, using immunocytochemical techniques (such as immunofluorescent staining, glucose oxidase and colloidal gold labeling) in light and electron microscopy; (b) to develop a tissue embedding method so that serial sections can be made for histopathological and immunocytochemical staining for use both in light and electron microscopy; (c) to determine whether there is any difference in the preferential location of bacterial proliferation in host tissues and, in particular, the role of the macrophages in salmonellosis, by comparing genetically resistant versus susceptible mice infected with salmonellae. The project is considered as a crucial step in the elucidation of pathogenesis of and immunity in murine salmonellosis, particularly in view of the current interest in the genetic variations of host response to infection. Such a definitive study is essential in providing the basis for the development of salmonella vaccines.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI019434-04
Application #
3128791
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1984-09-30
Project End
1989-12-31
Budget Start
1988-01-01
Budget End
1988-12-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Type
Overall Medical
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
Xu, H R; Tan, Y Y; Hsu, H S et al. (1993) Comparative antibody response to Salmonella antigens in genetically resistant and susceptible mice. Clin Exp Immunol 91:73-7
Xu, H R; Hsu, H S; Moncure, C W et al. (1993) Correlation of antibody titres induced by vaccination with protection in mouse typhoid. Vaccine 11:725-9
Xu, H R; Hsu, H S (1992) Dissemination and proliferation of Salmonella typhimurium in genetically resistant and susceptible mice. J Med Microbiol 36:377-81
Ding, H F; Nakoneczna, I; Hsu, H S (1990) Protective immunity induced in mice by detoxified salmonella lipopolysaccharide. J Med Microbiol 31:95-102
Hsu, H S (1989) Pathogenesis and immunity in murine salmonellosis. Microbiol Rev 53:390-409
Lin, F R; Hsu, H S; Mumaw, V R et al. (1989) Confirmation of destruction of salmonellae within murine peritoneal exudate cells by immunocytochemical technique. Immunology 67:394-400
Lin, F R; Hsu, H S; Mumaw, V R et al. (1989) Intracellular destruction of salmonellae in genetically resistant mice. J Med Microbiol 30:79-87
Wang, X M; Lin, F R; Hsu, H S et al. (1988) Electronmicroscopic studies on the location of salmonella proliferation in the murine spleen. J Med Microbiol 25:41-7
Lin, F R; Wang, X M; Hsu, H S et al. (1987) Electron microscopic studies on the location of bacterial proliferation in the liver in murine salmonellosis. Br J Exp Pathol 68:539-50
Guo, Y N; Hsu, H S; Mumaw, V R et al. (1986) Electronmicroscopy studies on the opsonic role of antiserum and the subsequent destruction of Salmonellae within murine inflammatory leukocytes. J Med Microbiol 22:343-9