Facultative intracellular pathogens continue to pose an important threat to human health, particularly in those whose resistance is impaired by some underlying immunodeficiency. Formerly it was thought that protective immunity against this group of pathogens depended chiefly on T helper cell activation of macrophage bactericidal activity. More recently, it has become evident that there are additional cellular and molecular interactions that substantially influence the pathogenesis of these infections. Murine listeriosis has provided a valuable model for investigating host defense mechanisms to facultative intracellular pathogens. Previous work from our laboratory has demonstrated that several soluble mediators (cytokines) are capable of substantially augmenting host defense. In addition, studies in this and other laboratories have differentiated the contributions of T cell subpopulations to host defense. There are two overall objectives of the research proposed in this application. The first is to understand the integration of cytokines and T cell subsets in cellular immunity against bacterial infection. This will be addressed by in vivo experiments that will use immunocytochemistry to identify T cell subpopulations infiltrating foci of infection, and immunocytochemistry and in situ hybridization to elucidate the profile of cytokines produced by these cells at various times during the course of the infection. This information will be correlated with bacteriological and pathological evaluations of the progression of the protective host response. The second overall objective will be to study in detail the cytolytic activity of spleen cells, obtained from listeria-immunized mice, for listeria-infected macrophages in vitro. The nature of the cytolytic cells, and the mediators required for the afferent and efferent aims of the cytolytic response will be determined. Experiments will also be performed to evaluate the contributions of cytolytic cells to host defense in vivo. Besides being of value as a general model for the immunoregulation of resistance to facultative intracellular pathogens, the information obtained will also increase our understanding of the pathogenesis of listeriosis, which has emerged as a significant public health threat.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI021343-08
Application #
3131357
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1984-07-01
Project End
1993-12-31
Budget Start
1992-01-01
Budget End
1992-12-31
Support Year
8
Fiscal Year
1992
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
Czuprynski, C J; Noel, E J; Adlam, C (1991) Pasteurella haemolytica A1 purified capsular polysaccharide does not stimulate interleukin-1 and tumor necrosis factor release by bovine monocytes and alveolar macrophages. Vet Immunol Immunopathol 28:157-63

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