Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI015613-07
Application #
3126281
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1978-12-01
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
7
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Temple University
Department
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19122

  Publications

Eisenstein, T K (2001) Implications of Salmonella-induced nitric oxide (NO) for host defense and vaccines: NO, an antimicrobial, antitumor, immunosuppressive and immunoregulatory molecule. Microbes Infect 3:1223-31
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
Schwacha, M G; Meissler Jr, J J; Eisenstein, T K (1998) Salmonella typhimurium infection in mice induces nitric oxide-mediated immunosuppression through a natural killer cell-dependent pathway. Infect Immun 66:5862-6
Eisenstein, T K; Meissler Jr, J J; Miller, S I et al. (1998) Immunosuppression and nitric oxide production induced by parenteral live Salmonella vaccines do not correlate with protective capacity: a phoP::Tn10 mutant does not suppress but does protect. Vaccine 16:24-32
MacFarlane, A S; Huang, D; Schwacha, M G et al. (1998) Nitric oxide mediates immunosuppression induced by Listeria monocytogenes infection: quantitative studies. Microb Pathog 25:267-77
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
Wallace, P K; Eisenstein, T K; Meissler Jr, J J et al. (1995) Decreases in macrophage mediated antitumor activity with aging. Mech Ageing Dev 77:169-84
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

Showing the most recent 10 out of 25 publications