Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1998 May;94(1):14–21. doi: 10.1046/j.1365-2567.1998.00477.x

Administration of killed bacteria together with listeriolysin O induces protective immunity against Listeria monocytogenes in mice.

H Xiong 1, Y Tanabe 1, S Ohya 1, M Mitsuyama 1
PMCID: PMC1364325  PMID: 9708181

Abstract

It is known that only listeriolysin O (LLO)-producing Listeria monocytogenes strains are able to induce protective immunity, but the underlining relationship between LLO produced by virulent strains and generation of protective immunity in the infected host remains poorly understood. In the present study, it was found that LLO gene expression was only detected in the mice infected with virulent strain which was able to induce protective immunity, while non-virulent strains or killed bacteria were not able to generate protective immunity. When mice were immunized with LLO plus killed bacteria in the presence of incomplete Freund's adjuvant, the protective immunity was partially generated, and adoptive transfer experiment confirmed that this protection was antigen specific. Reverse-transcription polymerase chain reaction revealed that LLO plus killed bacteria induced the expression of interferon-gamma (IFN-gamma) and interleukin-12 (IL-12). Our results also showed CD4+ T cells were the principal cells constituting protective immunity. Taken together, it may be concluded that LLO produced from virulent strains of L. monocytogenes was essential for the generation of protective immunity, and that LLO plus killed bacteria induced IFN-gamma and IL-12 expression which resulted in the generation of protective immunity.

Full text

PDF
14

Images in this article

17Figure 2
on p.17
19Figure 6
on p.19

Selected References

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

  1. Bradley L. M., Dalton D. K., Croft M. A direct role for IFN-gamma in regulation of Th1 cell development. J Immunol. 1996 Aug 15;157(4):1350–1358. [PubMed] [Google Scholar]
  2. Chen Y., Nakane A., Minagawa T. Recombinant murine gamma interferon induces enhanced resistance to Listeria monocytogenes infection in neonatal mice. Infect Immun. 1989 Aug;57(8):2345–2349. doi: 10.1128/iai.57.8.2345-2349.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cooper A. M., Roberts A. D., Rhoades E. R., Callahan J. E., Getzy D. M., Orme I. M. The role of interleukin-12 in acquired immunity to Mycobacterium tuberculosis infection. Immunology. 1995 Mar;84(3):423–432. [PMC free article] [PubMed] [Google Scholar]
  4. Cossart P., Vicente M. F., Mengaud J., Baquero F., Perez-Diaz J. C., Berche P. Listeriolysin O is essential for virulence of Listeria monocytogenes: direct evidence obtained by gene complementation. Infect Immun. 1989 Nov;57(11):3629–3636. doi: 10.1128/iai.57.11.3629-3636.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Czuprynski C. J., Haak-Frendscho M., Maroushek N., Brown J. F. Effects of recombinant human interleukin-6 alone and in combination with recombinant interleukin-1 alpha and tumor necrosis factor alpha on antibacterial resistance in mice. Antimicrob Agents Chemother. 1992 Jan;36(1):68–70. doi: 10.1128/aac.36.1.68. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dunn P. L., North R. J. Early gamma interferon production by natural killer cells is important in defense against murine listeriosis. Infect Immun. 1991 Sep;59(9):2892–2900. doi: 10.1128/iai.59.9.2892-2900.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Farber J. M., Peterkin P. I. Listeria monocytogenes, a food-borne pathogen. Microbiol Rev. 1991 Sep;55(3):476–511. doi: 10.1128/mr.55.3.476-511.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gaillard J. L., Berche P., Frehel C., Gouin E., Cossart P. Entry of L. monocytogenes into cells is mediated by internalin, a repeat protein reminiscent of surface antigens from gram-positive cocci. Cell. 1991 Jun 28;65(7):1127–1141. doi: 10.1016/0092-8674(91)90009-n. [DOI] [PubMed] [Google Scholar]
  9. Gaillard J. L., Berche P., Sansonetti P. Transposon mutagenesis as a tool to study the role of hemolysin in the virulence of Listeria monocytogenes. Infect Immun. 1986 Apr;52(1):50–55. doi: 10.1128/iai.52.1.50-55.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Garside P., Mowat A. M. Polarization of Th-cell responses: a phylogenetic consequence of nonspecific immune defence? Immunol Today. 1995 May;16(5):220–223. doi: 10.1016/0167-5699(95)80162-6. [DOI] [PubMed] [Google Scholar]
  11. Gellin B. G., Broome C. V. Listeriosis. JAMA. 1989 Mar 3;261(9):1313–1320. [PubMed] [Google Scholar]
  12. Harty J. T., Bevan M. J. Specific immunity to Listeria monocytogenes in the absence of IFN gamma. Immunity. 1995 Jul;3(1):109–117. doi: 10.1016/1074-7613(95)90163-9. [DOI] [PubMed] [Google Scholar]
  13. Hsieh B., Schrenzel M. D., Mulvania T., Lepper H. D., DiMolfetto-Landon L., Ferrick D. A. In vivo cytokine production in murine listeriosis. Evidence for immunoregulation by gamma delta+ T cells. J Immunol. 1996 Jan 1;156(1):232–237. [PubMed] [Google Scholar]
  14. Iizawa Y., Brown J. F., Czuprynski C. J. Early expression of cytokine mRNA in mice infected with Listeria monocytogenes. Infect Immun. 1992 Oct;60(10):4068–4073. doi: 10.1128/iai.60.10.4068-4073.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kathariou S., Metz P., Hof H., Goebel W. Tn916-induced mutations in the hemolysin determinant affecting virulence of Listeria monocytogenes. J Bacteriol. 1987 Mar;169(3):1291–1297. doi: 10.1128/jb.169.3.1291-1297.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kawamura I., Tsukada H., Yoshikawa H., Fujita M., Nomoto K., Mitsuyama M. IFN-gamma-producing ability as a possible marker for the protective T cells against Mycobacterium bovis BCG in mice. J Immunol. 1992 May 1;148(9):2887–2893. [PubMed] [Google Scholar]
  17. Koga T., Mitsuyama M., Handa T., Yayama T., Muramori K., Nomoto K. Induction by killed Listeria monocytogenes of effector T cells mediating delayed-type hypersensitivity but not protection in mice. Immunology. 1987 Oct;62(2):241–248. [PMC free article] [PubMed] [Google Scholar]
  18. Kuhn M., Goebel W. Induction of cytokines in phagocytic mammalian cells infected with virulent and avirulent Listeria strains. Infect Immun. 1994 Feb;62(2):348–356. doi: 10.1128/iai.62.2.348-356.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Köhler S., Bubert A., Vogel M., Goebel W. Expression of the iap gene coding for protein p60 of Listeria monocytogenes is controlled on the posttranscriptional level. J Bacteriol. 1991 Aug;173(15):4668–4674. doi: 10.1128/jb.173.15.4668-4674.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Langermans J. A., van der Hulst M. E., Nibbering P. H., van Furth R. Endogenous tumor necrosis factor alpha is required for enhanced antimicrobial activity against Toxoplasma gondii and Listeria monocytogenes in recombinant gamma interferon-treated mice. Infect Immun. 1992 Dec;60(12):5107–5112. doi: 10.1128/iai.60.12.5107-5112.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Liu W., Kurlander R. J. Analysis of the interrelationship between IL-12, TNF-alpha, and IFN-gamma production during murine listeriosis. Cell Immunol. 1995 Jul;163(2):260–267. doi: 10.1006/cimm.1995.1125. [DOI] [PubMed] [Google Scholar]
  22. Locksley R. M. Interleukin 12 in host defense against microbial pathogens. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5879–5880. doi: 10.1073/pnas.90.13.5879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Macatonia S. E., Hsieh C. S., Murphy K. M., O'Garra A. Dendritic cells and macrophages are required for Th1 development of CD4+ T cells from alpha beta TCR transgenic mice: IL-12 substitution for macrophages to stimulate IFN-gamma production is IFN-gamma-dependent. Int Immunol. 1993 Sep;5(9):1119–1128. doi: 10.1093/intimm/5.9.1119. [DOI] [PubMed] [Google Scholar]
  24. Magram J., Connaughton S. E., Warrier R. R., Carvajal D. M., Wu C. Y., Ferrante J., Stewart C., Sarmiento U., Faherty D. A., Gately M. K. IL-12-deficient mice are defective in IFN gamma production and type 1 cytokine responses. Immunity. 1996 May;4(5):471–481. doi: 10.1016/s1074-7613(00)80413-6. [DOI] [PubMed] [Google Scholar]
  25. Miller M. A., Skeen M. J., Ziegler H. K. Nonviable bacterial antigens administered with IL-12 generate antigen-specific T cell responses and protective immunity against Listeria monocytogenes. J Immunol. 1995 Nov 15;155(10):4817–4828. [PubMed] [Google Scholar]
  26. Mitsuyama M., Handa T., Koga T., Watanabe Y., Yayama T., Muramori K., Nomoto K. In vitro primary induction of T cells mediating delayed footpad reaction and acquired cellular resistance to Listeria monocytogenes. Immunobiology. 1988 Jul;177(3):254–266. doi: 10.1016/S0171-2985(88)80045-7. [DOI] [PubMed] [Google Scholar]
  27. Nakane A., Numata A., Minagawa T. Endogenous tumor necrosis factor, interleukin-6, and gamma interferon levels during Listeria monocytogenes infection in mice. Infect Immun. 1992 Feb;60(2):523–528. doi: 10.1128/iai.60.2.523-528.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Nishibori T., Cooray K., Xiong H., Kawamura I., Fujita M., Mitsuyama M. Correlation between the presence of virulence-associated genes as determined by PCR and actual virulence to mice in various strains of Listeria spp. Microbiol Immunol. 1995;39(5):343–349. doi: 10.1111/j.1348-0421.1995.tb02211.x. [DOI] [PubMed] [Google Scholar]
  29. Nishibori T., Xiong H., Kawamura I., Arakawa M., Mitsuyama M. Induction of cytokine gene expression by listeriolysin O and roles of macrophages and NK cells. Infect Immun. 1996 Aug;64(8):3188–3195. doi: 10.1128/iai.64.8.3188-3195.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Pernis A., Gupta S., Gollob K. J., Garfein E., Coffman R. L., Schindler C., Rothman P. Lack of interferon gamma receptor beta chain and the prevention of interferon gamma signaling in TH1 cells. Science. 1995 Jul 14;269(5221):245–247. doi: 10.1126/science.7618088. [DOI] [PubMed] [Google Scholar]
  31. Portnoy D. A., Jacks P. S., Hinrichs D. J. Role of hemolysin for the intracellular growth of Listeria monocytogenes. J Exp Med. 1988 Apr 1;167(4):1459–1471. doi: 10.1084/jem.167.4.1459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Poston R. M., Kurlander R. J. Cytokine expression in vivo during murine listeriosis. Infection with live, virulent bacteria is required for monokine and lymphokine messenger RNA accumulation in the spleen. J Immunol. 1992 Nov 1;149(9):3040–3044. [PubMed] [Google Scholar]
  33. Raveneau J., Geoffroy C., Beretti J. L., Gaillard J. L., Alouf J. E., Berche P. Reduced virulence of a Listeria monocytogenes phospholipase-deficient mutant obtained by transposon insertion into the zinc metalloprotease gene. Infect Immun. 1992 Mar;60(3):916–921. doi: 10.1128/iai.60.3.916-921.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Schmitt E., Hoehn P., Huels C., Goedert S., Palm N., Rüde E., Germann T. T helper type 1 development of naive CD4+ T cells requires the coordinate action of interleukin-12 and interferon-gamma and is inhibited by transforming growth factor-beta. Eur J Immunol. 1994 Apr;24(4):793–798. doi: 10.1002/eji.1830240403. [DOI] [PubMed] [Google Scholar]
  35. Scott P., Natovitz P., Coffman R. L., Pearce E., Sher A. Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens. J Exp Med. 1988 Nov 1;168(5):1675–1684. doi: 10.1084/jem.168.5.1675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Skeen M. J., Miller M. A., Shinnick T. M., Ziegler H. K. Regulation of murine macrophage IL-12 production. Activation of macrophages in vivo, restimulation in vitro, and modulation by other cytokines. J Immunol. 1996 Feb 1;156(3):1196–1206. [PubMed] [Google Scholar]
  37. Song F., Matsuzaki G., Mitsuyama M., Nomoto K. Differential effects of viable and killed bacteria on IL-12 expression of macrophages. J Immunol. 1996 Apr 15;156(8):2979–2984. [PubMed] [Google Scholar]
  38. Song F., Matsuzaki G., Mitsuyama M., Nomoto K. In vitro generation of IFN-gamma-producing Listeria-specific T cells is dependent on IFN-gamma production by non-NK cells. Cell Immunol. 1995 Feb;160(2):211–216. doi: 10.1016/0008-8749(95)80030-m. [DOI] [PubMed] [Google Scholar]
  39. Tsukada H., Kawamura I., Arakawa M., Nomoto K., Mitsuyama M. Dissociated development of T cells mediating delayed-type hypersensitivity and protective T cells against Listeria monocytogenes and their functional difference in lymphokine production. Infect Immun. 1991 Oct;59(10):3589–3595. doi: 10.1128/iai.59.10.3589-3595.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wagner R. D., Steinberg H., Brown J. F., Czuprynski C. J. Recombinant interleukin-12 enhances resistance of mice to Listeria monocytogenes infection. Microb Pathog. 1994 Sep;17(3):175–186. doi: 10.1006/mpat.1994.1064. [DOI] [PubMed] [Google Scholar]
  41. Xiong H., Kawamura I., Nishibori T., Mitsuyama M. Cytokine gene expression in mice at an early stage of infection with various strains of Listeria spp. differing in virulence. Infect Immun. 1994 Sep;62(9):3649–3654. doi: 10.1128/iai.62.9.3649-3654.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Xiong H., Kawamura I., Nishibori T., Mitsuyama M. Suppression of IFN-gamma production from Listeria monocytogenes-specific T cells by endogenously produced nitric oxide. Cell Immunol. 1996 Aug 25;172(1):118–125. doi: 10.1006/cimm.1996.0222. [DOI] [PubMed] [Google Scholar]
  43. von Koenig C. H., Finger H., Hof H. Failure of killed Listeria monocytogenes vaccine to produce protective immunity. Nature. 1982 May 20;297(5863):233–234. doi: 10.1038/297233a0. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES