Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1996 Jan;64(1):222–229. doi: 10.1128/iai.64.1.222-229.1996

The Salmonella dublin virulence plasmid does not modulate early T-cell responses in mice.

L A Guilloteau 1, A J Lax 1, S MacIntyre 1, T S Wallis 1
PMCID: PMC173749  PMID: 8557343

Abstract

The virulence plasmid in Salmonella dublin mediates systemic infection in mice and cattle. The role of gamma delta T cells or hepatic extrathymic T cells has recently been reported to be important in the control of the early stage of Salmonella choleraesuis infections of mice. Here, we report on T-cell responses in conventional mice after challenge with a virulent strain of S. dublin carrying a virulence plasmid or with a strain cured of the plasmid. Over a period of 4 days postinfection, when both strains could be compared, similar changes in alpha beta and gamma delta T-cell subsets in peritoneal cavities, livers, and spleens were recorded, demonstrating no clear role of the virulence plasmid in modulation of early T-cell responses. To investigate further the role of the virulence plasmid in pathogenesis, the growth of the plasmid-cured strain was assessed in SCID, SCID bg, and irradiated mice. During the first 6 days after infection, there was no statistically difference in the net growth of Salmonella cells in the livers and spleens of SCID and SCID bg mice compared with conventional BALB/mice. This observation excludes a key role for a T- or B-cell-mediated immune response in controlling the initial growth of the plasmid-cured S. dublin strain. Thereafter, the immunocompromised mice were no longer able to control infection, although SCID mice were more efficient at controlling net bacterial multiplication than SCID bg mice, potentially implicating NK cells in the control of infection in SCID mice. The early control of net bacterial multiplication in the spleens and livers of BALB/c mice was ablated by whole-body X-irradiation. Both wild-type and plasmid-cured strains multiplied significantly more rapidly in irradiated than in conventional BALB/c mice. However, the numbers of wild-type bacterial still increased more rapidly than in the numbers of the cured strains. These results are consistent with a role of the S. dublin virulence plasmid in promoting in vivo growth of Salmonella cells.

Full Text

The Full Text of this article is available as a PDF (319.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akeda H., Mitsuyama M., Tatsukawa K., Nomoto K., Takeya K. The synergistic contribution of macrophages and antibody to protection against Salmonella typhimurium during the early phase of infection. J Gen Microbiol. 1981 Apr;123(2):209–214. doi: 10.1099/00221287-123-2-209. [DOI] [PubMed] [Google Scholar]
  2. Austyn J. M., Gordon S. F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur J Immunol. 1981 Oct;11(10):805–815. doi: 10.1002/eji.1830111013. [DOI] [PubMed] [Google Scholar]
  3. Baird G. D., Manning E. J., Jones P. W. Evidence for related virulence sequences in plasmids of Salmonella dublin and Salmonella typhimurium. J Gen Microbiol. 1985 Jul;131(7):1815–1823. doi: 10.1099/00221287-131-7-1815. [DOI] [PubMed] [Google Scholar]
  4. Bosma G. C., Custer R. P., Bosma M. J. A severe combined immunodeficiency mutation in the mouse. Nature. 1983 Feb 10;301(5900):527–530. doi: 10.1038/301527a0. [DOI] [PubMed] [Google Scholar]
  5. Colwell D. E., Michalek S. M., McGhee J. R. Lps gene regulation of mucosal immunity and susceptibility to Salmonella infection in mice. Curr Top Microbiol Immunol. 1986;124:121–147. doi: 10.1007/978-3-642-70986-9_8. [DOI] [PubMed] [Google Scholar]
  6. Croy B. A., Chapeau C. Evaluation of the pregnancy immunotrophism hypothesis by assessment of the reproductive performance of young adult mice of genotype scid/scid.bg/bg. J Reprod Fertil. 1990 Jan;88(1):231–239. doi: 10.1530/jrf.0.0880231. [DOI] [PubMed] [Google Scholar]
  7. Emoto M., Danbara H., Yoshikai Y. Induction of gamma/delta T cells in murine salmonellosis by an avirulent but not by a virulent strain of Salmonella choleraesuis. J Exp Med. 1992 Aug 1;176(2):363–372. doi: 10.1084/jem.176.2.363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Emoto M., Naito T., Nakamura R., Yoshikai Y. Different appearance of gamma delta T cells during salmonellosis between Ityr and Itys mice. J Immunol. 1993 Apr 15;150(8 Pt 1):3411–3420. [PubMed] [Google Scholar]
  9. Gordon S., Fraser I., Nath D., Hughes D., Clarke S. Macrophages in tissues and in vitro. Curr Opin Immunol. 1992 Feb;4(1):25–32. doi: 10.1016/0952-7915(92)90119-y. [DOI] [PubMed] [Google Scholar]
  10. Griggs N. D., Smith R. A. Adoptive transfer of natural killer cell activity in B6D2F1 mice challenged with Salmonella typhimurium. Cell Immunol. 1991 Jun;135(1):88–94. doi: 10.1016/0008-8749(91)90256-b. [DOI] [PubMed] [Google Scholar]
  11. Guilloteau L., Buzoni-Gatel D., Blaise F., Bernard F., Pépin M. Phenotypic analysis of splenic lymphocytes and immunohistochemical study of hepatic granulomas after a murine infection with Salmonella abortusovis. Immunology. 1991 Dec;74(4):630–637. [PMC free article] [PubMed] [Google Scholar]
  12. Gulig P. A., Curtiss R., 3rd Plasmid-associated virulence of Salmonella typhimurium. Infect Immun. 1987 Dec;55(12):2891–2901. doi: 10.1128/iai.55.12.2891-2901.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gulig P. A., Danbara H., Guiney D. G., Lax A. J., Norel F., Rhen M. Molecular analysis of spv virulence genes of the Salmonella virulence plasmids. Mol Microbiol. 1993 Mar;7(6):825–830. doi: 10.1111/j.1365-2958.1993.tb01172.x. [DOI] [PubMed] [Google Scholar]
  14. Gulig P. A., Doyle T. J. The Salmonella typhimurium virulence plasmid increases the growth rate of salmonellae in mice. Infect Immun. 1993 Feb;61(2):504–511. doi: 10.1128/iai.61.2.504-511.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gulig P. A. Virulence plasmids of Salmonella typhimurium and other salmonellae. Microb Pathog. 1990 Jan;8(1):3–11. doi: 10.1016/0882-4010(90)90003-9. [DOI] [PubMed] [Google Scholar]
  16. Heffernan E. J., Fierer J., Chikami G., Guiney D. Natural history of oral Salmonella dublin infection in BALB/c mice: effect of an 80-kilobase-pair plasmid on virulence. J Infect Dis. 1987 Jun;155(6):1254–1259. doi: 10.1093/infdis/155.6.1254. [DOI] [PubMed] [Google Scholar]
  17. Hoertt B. E., Ou J., Kopecko D. J., Baron L. S., Warren R. L. Novel virulence properties of the Salmonella typhimurium virulence-associated plasmid: immune suppression and stimulation of splenomegaly. Plasmid. 1989 Jan;21(1):48–58. doi: 10.1016/0147-619x(89)90086-3. [DOI] [PubMed] [Google Scholar]
  18. Hormaeche C. E., Mastroeni P., Arena A., Uddin J., Joysey H. S. T cells do not mediate the initial suppression of a Salmonella infection in the RES. Immunology. 1990 Jun;70(2):247–250. [PMC free article] [PubMed] [Google Scholar]
  19. Hormaeche C. E. The natural resistance of radiation chimeras to S. typhimurium C5. Immunology. 1979 Jun;37(2):329–332. [PMC free article] [PubMed] [Google Scholar]
  20. Izhar M., DeSilva L., Joysey H. S., Hormaeche C. E. Moderate immunodeficiency does not increase susceptibility to Salmonella typhimurium aroA live vaccines in mice. Infect Immun. 1990 Jul;58(7):2258–2261. doi: 10.1128/iai.58.7.2258-2261.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lax A. J., Pullinger G. D., Baird G. D., Williamson C. M. The virulence plasmid of Salmonella dublin: detailed restriction map and analysis by transposon mutagenesis. J Gen Microbiol. 1990 Jun;136(6):1117–1123. doi: 10.1099/00221287-136-6-1117. [DOI] [PubMed] [Google Scholar]
  22. Maier T., Oels H. C. Role of the macrophage in natural resistance to salmonellosis in mice. Infect Immun. 1972 Oct;6(4):438–443. doi: 10.1128/iai.6.4.438-443.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Manning E. J., Baird G. D., Jones P. W. The role of plasmid genes in the pathogenicity of Salmonella dublin. J Med Microbiol. 1986 May;21(3):239–243. doi: 10.1099/00222615-21-3-239. [DOI] [PubMed] [Google Scholar]
  24. Maskell D. J., Hormaeche C. E., Harrington K. A., Joysey H. S., Liew F. Y. The initial suppression of bacterial growth in a salmonella infection is mediated by a localized rather than a systemic response. Microb Pathog. 1987 Apr;2(4):295–305. doi: 10.1016/0882-4010(87)90127-6. [DOI] [PubMed] [Google Scholar]
  25. Matsumoto Y., Emoto M., Usami J., Maeda K., Yoshikai Y. A protective role of extrathymic alpha beta TcR cells in the liver in primary murine salmonellosis. Immunology. 1994 Jan;81(1):8–14. [PMC free article] [PubMed] [Google Scholar]
  26. Mixter P. F., Camerini V., Stone B. J., Miller V. L., Kronenberg M. Mouse T lymphocytes that express a gamma delta T-cell antigen receptor contribute to resistance to Salmonella infection in vivo. Infect Immun. 1994 Oct;62(10):4618–4621. doi: 10.1128/iai.62.10.4618-4621.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nauciel C. Role of CD4+ T cells and T-independent mechanisms in acquired resistance to Salmonella typhimurium infection. J Immunol. 1990 Aug 15;145(4):1265–1269. [PubMed] [Google Scholar]
  28. O'Brien A. D. Influence of host genes on resistance of inbred mice to lethal infection with Salmonella typhimurium. Curr Top Microbiol Immunol. 1986;124:37–48. [PubMed] [Google Scholar]
  29. O'Brien A. D., Metcalf E. S. Control of early Salmonella typhimurium growth in innately Salmonella-resistant mice does not require functional T lymphocytes. J Immunol. 1982 Oct;129(4):1349–1351. [PubMed] [Google Scholar]
  30. Pardon P., Popoff M. Y., Coynault C., Marly J., Miras I. Virulence-associated plasmids of Salmonella serotype Typhimurium in experimental murine infection. Ann Inst Pasteur Microbiol. 1986 Jul-Aug;137B(1):47–60. doi: 10.1016/s0769-2609(86)80093-x. [DOI] [PubMed] [Google Scholar]
  31. Ramarathinam L., Niesel D. W., Klimpel G. R. Salmonella typhimurium induces IFN-gamma production in murine splenocytes. Role of natural killer cells and macrophages. J Immunol. 1993 May 1;150(9):3973–3981. [PubMed] [Google Scholar]
  32. Riikonen P., Mäkelä P. H., Saarilahti H., Sukupolvi S., Taira S., Rhen M. The virulence plasmid does not contribute to growth of Salmonella in cultured murine macrophages. Microb Pathog. 1992 Oct;13(4):281–291. doi: 10.1016/0882-4010(92)90038-p. [DOI] [PubMed] [Google Scholar]
  33. Roder J., Duwe A. The beige mutation in the mouse selectively impairs natural killer cell function. Nature. 1979 Mar 29;278(5703):451–453. doi: 10.1038/278451a0. [DOI] [PubMed] [Google Scholar]
  34. Skeen M. J., Ziegler H. K. Induction of murine peritoneal gamma/delta T cells and their role in resistance to bacterial infection. J Exp Med. 1993 Sep 1;178(3):971–984. doi: 10.1084/jem.178.3.971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Skeen M. J., Ziegler H. K. Intercellular interactions and cytokine responsiveness of peritoneal alpha/beta and gamma/delta T cells from Listeria-infected mice: synergistic effects of interleukin 1 and 7 on gamma/delta T cells. J Exp Med. 1993 Sep 1;178(3):985–996. doi: 10.1084/jem.178.3.985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Spicer S. S., Sato A., Vincent R., Eguchi M., Poon K. C. Lysosome enlargement in the Chediak-Higashi syndrome. Fed Proc. 1981 Apr;40(5):1451–1455. [PubMed] [Google Scholar]
  37. Springer T., Galfré G., Secher D. S., Milstein C. Mac-1: a macrophage differentiation antigen identified by monoclonal antibody. Eur J Immunol. 1979 Apr;9(4):301–306. doi: 10.1002/eji.1830090410. [DOI] [PubMed] [Google Scholar]
  38. Strahan K., Chatfield S. N., Tite J., Dougan G., Hormaeche C. E. Impaired resistance to infection does not increase the virulence of Salmonella htrA live vaccines for mice. Microb Pathog. 1992 Apr;12(4):311–317. doi: 10.1016/0882-4010(92)90049-t. [DOI] [PubMed] [Google Scholar]
  39. Wallis T. S., Paulin S. M., Plested J. S., Watson P. R., Jones P. W. The Salmonella dublin virulence plasmid mediates systemic but not enteric phases of salmonellosis in cattle. Infect Immun. 1995 Jul;63(7):2755–2761. doi: 10.1128/iai.63.7.2755-2761.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Williamson C. M., Pullinger G. D., Lax A. J. Identification of an essential virulence region on Salmonella plasmids. Microb Pathog. 1988 Dec;5(6):469–473. doi: 10.1016/0882-4010(88)90008-3. [DOI] [PubMed] [Google Scholar]
  41. van Dissel J. T., Stikkelbroeck J. J., Sluiter W., Leijh P. C., van Furth R. Differences in initial rate of intracellular killing of Salmonella typhimurium by granulocytes of Salmonella-susceptible C57BL/10 mice and Salmonella-resistant CBA mice. J Immunol. 1986 Feb 1;136(3):1074–1080. [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES