Three mouse strains in the C3H lineage, C3H/HeJ, C3HeB/FeJ and C3H/HeNCr1BR, which differ in their responsiveness of LPS and their innate susceptibilities to Salmonella infection, will be used to investigate immunity to Salmonella infection induced by a live, a virulent vaccine strain, SL3235, that is of a class of mutants being considered for development of a new vaccine for human typhoid fever. The mechanisms by which the vaccine results in specific resistance to virulent Salmonella infection will be assessed, as will the immunomodulation induced by this organism. The degree of macrophage activation to tumoricidal and microbicidal capacity will be compared with that engendered by killed Salmonella, BCG and C. parvum. The role of suppressor macrophages in modulating the humoral and cellular arms of the immune response will be investigated, as will molecular correlates of macrophage activation and suppression as measured by production of PGE-2, IL-1, H202, and 02. These studies should provide basic information on immunity to Salmonella infection, evaluate the potential of SL3235 as an immunomodulating agent, and possibly provide insight into the nature of the defect in macrophages of C3H/HeJ mice.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI015613-08
Application #
3126282
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1978-12-01
Project End
1988-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
8
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Temple University
Department
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19122
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MacFarlane, A S; Schwacha, M G; Eisenstein, T K (1999) In vivo blockage of nitric oxide with aminoguanidine inhibits immunosuppression induced by an attenuated strain of Salmonella typhimurium, potentiates Salmonella infection, and inhibits macrophage and polymorphonuclear leukocyte influx into the spleen. Infect Immun 67:891-8
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Schwacha, M G; Eisenstein, T K (1997) Interleukin-12 is critical for induction of nitric oxide-mediated immunosuppression following vaccination of mice with attenuated Salmonella typhimurium. Infect Immun 65:4897-903
Huang, D; Schwacha, M G; Eisenstein, T K (1996) Attenuated Salmonella vaccine-induced suppression of murine spleen cell responses to mitogen is mediated by macrophage nitric oxide: quantitative aspects. Infect Immun 64:3786-92
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Eisenstein, T K (1994) Suppressor macrophages. Immunol Ser 60:203-24
Wu, L; Morahan, P S; Hendrzak, J A et al. (1994) Herpes simplex virus type 1 replication and IL-1 beta gene expression in mouse peritoneal macrophages activated in vivo by an attenuated Salmonella typhimurium vaccine or Corynebacterium parvum. Microb Pathog 16:387-99

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