Paradoxes of Immunity and Immunosuppression in Salmonella Infection

  • Toby K. Eisenstein
  • Niloofer Dalal
  • Loran Killar
  • Joo-Chiang Lee
  • Rosana Schafer
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 239)


There is continuing interest in mechanisms of immunity to systemic Salmonella infection, as concepts regarding the relative contributions of humoral and cellular immunity to host defense against these organisms form the theoretical basis for development of improved vaccines against typhoid fever (1,2). (Experimentally, investigations are carried out using a mouse model of systemic infection with Salmonella typhimurium as S. typhi is not virulent for mice.) Although the current typhoid vaccine, consisting of acetone-killed cells, has been shown to be protective in humans (3), it has an undesirable level of toxicity (1). Recent efforts have focused on live, attenuated strains of S. typhi which can be given orally, as an alternative vaccine strategy. A galE mutant, Ty21a, has been shown to have efficacy in a field trial in Egypt (4) although results have been less promising in field trials in Chile (5). One drawback of the Ty2la strain is that the exact nature of the genetic lesions which confer loss of virulence are not known (6). Stocker and colleagues have developed a series of mutants in various species of Salmonella which are blocked in aromatic synthesis due to transposon-mediated gene deletions or inversions (7,8). Based on high levels of protection induced in mouse models of typhoid fever using these aroAstrains of S. typhimurium Stocker has developed attenuated S. typhi with similar types of lesions for potential use in humans against typhoid fever (9). In addition, there is also considerable interest in using these aro-strains as vectors for cloned genes of other organisms such as E. coli enterotoxins (10,11).


Spleen Cell Typhoid Fever Peritoneal Cell SL3235 Cell Tumor Cytotoxicity 
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  1. 1.
    Edelman, R., and M. M. Levine, Summary of an international workshop on typhoid fever, Rev. Inf. Dis. 8: 329 (1986).CrossRefGoogle Scholar
  2. 2.
    Eisenstein, T. K., and B. M. Sultzer, Immunity to Salmonella infection, in: “Host Defenses to Intracellular Pathogens,” T. K. Eisenstein, P. Actor, and H. Friedman, eds., Plenum, New York (1983).CrossRefGoogle Scholar
  3. 3.
    Ashcroft, M. T, A seven year field trial of two typhoid vaccines in Guyana, Lancet 2: 1056 (1967).Google Scholar
  4. 4.
    Wandan, M. H., C. Sérié, Y. Cerisier, S. Sallam and R. Germanier, A controlled field trial of live Salmonella typhi strain Ty 21a oral vaccine against typhoid: three-year results, J. Inf. Dis. 145: 292 (1982).CrossRefGoogle Scholar
  5. 5.
    Levine, M. M., R. E. Black, C. Ferreccio, M. L. Clements, C. Lanata, J. Rooney, and Chilean Typhoid Committee, The efficacy of attenuated Salmonella typhi oral vaccine strain Ty2la evaluated in controlled field trials, in: “Proceedings of the Nobel Conference on Recent Advances in Vaccines and Drugs against Diarrhoeal Diseases, Stockholm, 3–6 June 1985,” J. Holmgren, A. Lindberg and R. Mollby, eds., Student Literatur, Gothenburg, Sweden (1986).Google Scholar
  6. 6.
    Silva, B. A., C. Gonzalez, G. C. Mora and F. Cabello, Genetic characteristics of the Salmonella typhi strain Ty2la vaccine, J. Inf. Dis. 155: 1077 (1987).CrossRefGoogle Scholar
  7. 7.
    Hoiseth, S. K., and B. A. D. Stocker, Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines, Nature 291: 238 (1981).Google Scholar
  8. 8.
    Smith, B. P., M. Reina-Guerra, B. A. D. Stocker, S. K. Hoiseth and E. Johnson, Aromatic-dependent Salmonella dublin as a parenteral modified live vaccine for calves, Am. J. Vet. Res. 45: 2231 (1984).PubMedGoogle Scholar
  9. 9.
    Levine, M. M., D. Herrington, J. R. Murphy, J. G. Morris, G. Losonsky, B. Tall, A. A. Lindberg, S. Svenson, S. Bagar, M. F. Edwards and B. Stocker, Safety, infectivity immunogenicity, and in vivo stability of two attenuated auxotrophic mutant strains of Salmonella typhi J. Clin. Invest. 79:888 (1987).Google Scholar
  10. 10.
    Clements, J. D., F. L. Lyon, K. L. Lowe, A. L. Farrand and S. El-Morshidy, Oral immunization of mice with attenuated Salmonella enteritidis containing a recombinant plasmid which codes for production of the B subunit of heat-labile Escherichia coli enterotoxin, Infect. Immun. 53:685 (1986).Google Scholar
  11. 11.
    Maskell, D., F. Y. Liew, K. Sweeney, G. Dougan and C. E. Hormaeche, Attenuated Salmonella typhimurium as live oral vaccines and carriers for delivering antigens to the secretory immune system, in: “Vaccines 86,” R. A. Lerner, R. Channock and F. Brown, eds., Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1986).Google Scholar
  12. 12.
    Eisenstein, T. K., L. M. Killar, B. A. D. Stocker and B. M. Sultzer, Cellular immunity induced by avirulent Salmonella in LPS-defective C3H/HeJ mice, J. Immunol. 133: 958 (1984).PubMedGoogle Scholar
  13. 13.
    Lee, J-C., C. W. Gibson and T. K. Eisenstein, Macrophage-mediated mito-genic suppression induced in mice of the C3H lineage by a vaccine strain of Salmonella typhimurium, Cell. Imnunol. 91:75 (1985).Google Scholar
  14. 14.
    Angerman, C. R., and T. K. Eisenstein, Comparative efficacy and toxicity of a ribosomal vaccine, acetone-killed cells, lipopolysaccharide, and a live cell vaccine prepared from Salmonella typhimurium, Infect. Immun. 19:575 (1978).Google Scholar
  15. 15.
    Eisenstein, T. K., L. W. Deakins, L. Killar, P. H. Saluk and B. M. Sultzer, Dissociation of innate susceptibility to Salmonella infection and endotoxin responsiveness in C3HeB/FeJ mice and other strains in the C3H lineage, Infect. Immun. 36:696 (1982).Google Scholar
  16. 16.
    Killar, L. M., and T. K. Eisenstein, Immunity to Salmonella typhimurium infection in C3H/HeJ and C3H/HeNCr1BR mice: studies with an aromatic-dependent live S. typhimurium strain as a vaccine, Infect. Immun. 47:605 (1985).Google Scholar
  17. 17.
    Freundlich, B., and N. Avdalovic, Use of gelatin/plasma coated flasks for isolating human peripheral blood monocytes, J. Immunol. Methods 62:31 (1983).Google Scholar
  18. 18.
    Ly, I. A., and R. I. Mishell, Separation of mouse spleen cells by passage through columns of Sephadex G-10, J. Immunol. Methods 5:239 (1974).Google Scholar
  19. 19.
    Cunningham, A. J., and A. Szenberg, Further improvements in the plaque technique for detecting single antibody-forming cells, Immunology 14: 599 (1968).Google Scholar
  20. 20.
    Mishell, R. I., and R. W. Dutton, Immunization of dissociated spleen cell cultures from normal mice, J. Exp. Med. 126: 423 (1967).PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Eisenstein, T. K., L. M. Killar and B. M. Sultzer, Immunity to infection with Salmonella typhimurium: mouse-strain differences in vaccine-and serum-mediated protection, J. Inf. Dis. 150: 425 (1984).CrossRefGoogle Scholar
  22. 22.
    Mackaness, G. B., The immunological basis of acquired cellular resistance, J. Exp. Med. 120: 105 (1964).PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Orme, I. M., and F. M. Collins, Adoptive protection of the Mycobacterium tuberculosis-infected lung. Dissociation between cells that passively transfer protective immunity and those that transfer delayed-type hypersensitivity to tuberculin, Cell. Immunol. 84:113 (1984).Google Scholar
  24. 24.
    Mackaness, G. B., and W. C. Hill, The effect of anti-lymphocyte globulin on cell-mediated resistance to infection, J. Exp. Med. 129: 993 (1969).PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Ruco, L. P., and M. S. Meltzer, Defective tumoricidal capacity of macrophages from C3H/HeJ mice. J. Immunol. 120: 329 (1978).PubMedGoogle Scholar
  26. 26.
    Wellhausen, S. R., and J. M. Mansfield, Characteristics of splenic suppressor cell-target-cell interaction in experimental Africal Trypanosomiasis, Cell. Immunol. 54:414 (1980).Google Scholar
  27. 27.
    Suzuki, Y., N. Watanaba and A. Kobayashi, Nonspecific suppression of primary antibody responses and the presence of plastic adherent suppressor cells in Toxoplasma gondii-infected mice, Infect. Immun. 34:30 (1981).Google Scholar
  28. 28.
    Tarleton, R. L., R. Schafer and R. E. Kuhn, Effects of extracts of Trypanosoma cruzi on immune responses: induction of a nonspecific suppressor factors, Infect. Immun. 41:978 (1983).Google Scholar
  29. 29.
    Shibata, Y., and A. Volkman, The effect of bone marrow depletion on prostaglandin E-producing suppressor macrophages in mouse spleen, J. Inmunol. 135: 3897 (1985).Google Scholar
  30. 30.
    Shibata, Y., and A. Volkman, The effect of hemopoietic microenvironment on splenic suppressor macrophages in congenitally anemic mice of genotype S1/Sld, J. Immunol. 135: 3905 (1985).PubMedGoogle Scholar
  31. 31.
    Hochadel, J. F., and K. F. Keller, Protective effects of passively transferred immune T- or B-lymphocytes in mice infected with Salmonella typhimurium J. Inf. Dis. 135: 813 (1977).CrossRefGoogle Scholar
  32. 32.
    Chander, R., K. B. Sainis and N. F. Lewis, Role of thymus-derived lymphocytes in acquired immunity to salmonellosis in mice, Microbiol. Immunol. 30:1299 (1986).Google Scholar
  33. 33.
    Smith, R. A., A. Esa and M. Stiff, Transfer of Salmonella resistance and delayed hypersensitivity with murine-derived transfer factor, Infect. Immun. 36:271 (1982).Google Scholar
  34. 34.
    Paul, C., K. Shalala, R. Warren and R. Smith, Adoptive transfer of murine host protection to salmonellosis with T-cell growth factor-dependent, Salmonella-specific T-cell lines, Infect. Immun. 48:40 (1985).Google Scholar
  35. 35.
    Ushiba, D., Two types of immunity in experimental typhoid; “cellular immunity” and “humoral immunity,” Keio J. Med. 14: 45 (1965).Google Scholar
  36. 36.
    Blanden, R. V., G. B. Mackaness and F. M. Collins, Mechanisms of acquired resistance in mouse typhoid, J. Exp. Med. 124: 585 (1966).PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Killar, L. M., and T. K. Eisenstein, Differences in delayed-type hypersensitivity responses in various mouse strains in the C3H lineage infected with Salmonella typhimurium strain SL3235, J. Immunol. 133: 1190 (1984).Google Scholar
  38. 38.
    Killar, L. M., and T. K. Eisenstein, Delayed-type hypersensitivity and immunity to Salmonella typhimurium, Infect. Immun. 52:504 (1986).Google Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Toby K. Eisenstein
    • 1
  • Niloofer Dalal
    • 1
  • Loran Killar
    • 1
  • Joo-Chiang Lee
    • 1
  • Rosana Schafer
    • 1
  1. 1.Department of Microbiology and ImmunologyTemple University School of MedicinePhiladelphiaUSA

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