Infections caused by facultative intracellular pathogens continue to be a significant health problem in the United States and througout the world. Immunotherapeutic strategies for combatting these infections would therefore be of considerable benefit. Murine listeriosis has proven to be a convenient, reproducible, and extremely informative laboratory model for studying immuno-regulation of resistance to infection by facultative intracellular pathogens. Considerable evidence has been provided by our laboratory and others linking anti-listeria resistance with the host's ability to rapidly mobilize an adequate inflammatory response against the invading bacteria. The dual role of T lymphocytes in the regulation of inflammatory responsiveness and antibacterial resistance has been indicated by adpotive transfer studies of listeria-immune T cells which showed that L3T4+ T cells mediate accumulation of inflammatory cells in vivo and Lyt2+ T cells are required for expression of antibacterial resistance. Although these studies have been quite informative, they fail to demonstrate the cellular interactions that occur in vivo when an individual first encounters an invading facultative intracellular pathogen. In the proposed study we will manipulate mouse T cell subsets in vivo by administration of monoclonal anti- L3T4 and anit Lyt2 antibodies and then determine the effect of these treatments on inflammatory responsiveness and antibacterial resistance. Soluble factors produced by these T cells will be assessed for their pro-inflammatory effects in vivo and for their influence on macrophage antibacterial activity in vitro. The possible cytotoxic actio of listeria-immune Lyt2+ T cells against literia-infected macrophages will be investigated as a potential mechanism explaining the protection mediated by these cells in vivo. Besides providing information that will further illuminate our general understanding of T cell-mediated resistance to facultative pathogens, the resuslts of this project will also be germane to the pathogenesis of human listeriosis, which has rapidly emerged as a significant public health problem due to ingestion of listeria-contaminated dairy products.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI021343-06
Application #
3131356
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1984-07-01
Project End
1990-12-31
Budget Start
1989-07-01
Budget End
1990-12-31
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Veterinary Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Boury, N M; Czuprynski, C J (1995) Listeria monocytogenes infection increases neutrophil adhesion and damage to a murine hepatocyte cell line in vitro. Immunol Lett 46:111-6
Wagner, R D; Maroushek, N M; Brown, J F et al. (1994) Treatment with anti-interleukin-10 monoclonal antibody enhances early resistance to but impairs complete clearance of Listeria monocytogenes infection in mice. Infect Immun 62:2345-53
Adams, J L; Czuprynski, C J (1994) Mycobacterial cell wall components induce the production of TNF-alpha, IL-1, and IL-6 by bovine monocytes and the murine macrophage cell line RAW 264.7. Microb Pathog 16:401-11
Czuprynski, C J; Brown, J F; Wagner, R D et al. (1994) Administration of antigranulocyte monoclonal antibody RB6-8C5 prevents expression of acquired resistance to Listeria monocytogenes infection in previously immunized mice. Infect Immun 62:5161-3
Czuprynski, C J; Brown, J F; Maroushek, N et al. (1994) Administration of anti-granulocyte mAb RB6-8C5 impairs the resistance of mice to Listeria monocytogenes infection. J Immunol 152:1836-46
Wagner, R D; Czuprynski, C J (1993) Cytokine mRNA expression in livers of mice infected with Listeria monocytogenes. J Leukoc Biol 53:525-31
Iizawa, Y; Wagner, R D; Czuprynski, C J (1993) Analysis of cytokine mRNA expression in Listeria-resistant C57BL/6 and Listeria-susceptible A/J mice during Listeria monocytogenes infection. Infect Immun 61:3739-44
Ortiz-Carranza, O; Czuprynski, C J (1992) Activation of bovine neutrophils by Pasteurella haemolytica leukotoxin is calcium dependent. J Leukoc Biol 52:558-64
Hamilton, H L; Czuprynski, C J (1992) Effects of mycobactin J and lactoferrin supplementation of drinking water on the in vivo multiplication of Mycobacterium paratuberculosis in gnotobiotic mice. Can J Vet Res 56:70-3
Hamilton, H L; Cooley, A J; Adams, J L et al. (1991) Mycobacterium paratuberculosis monoassociated nude mice as a paratuberculosis model. Vet Pathol 28:146-55

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