Skip to main content
Log in

In vivo neutralization of tumor necrosis factor-alpha and interferon-gamma abrogates resistance to Yersinia enterocolitica infection in mice

  • Original investigations
  • Published:
Medical Microbiology and Immunology Aims and scope Submit manuscript

Abstract

Cytokines are important mediators of the inflammatory host response against infectious agents. In this study, the role of tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) in the elimination of a primary infection with highly virulent Yersinia enterocolitica serotype 0:8 strain WA-P has been investigated in C57BL/6 mice. The injection of anti-TNF-α or anti-IFN-γ antibodies (“serotherapy”) prior to the intravenous challenge of a sublethal dose of Y. enterocolitica caused an increased bacterial net-growth in the spleens, although this effect was more pronounced for anti-TNF-α treatment. The later treatment with anti-TNF-α or anti-IFN-γ antibodies on day 3 post infection likewise abrogated resistance to Y. enterocolitica and, subsequently, led to death from progressive infection. Our data demonstrate for the first time that the endogenous production of both the cytokines TNF-α and IFN-γ is required for the restriction of a primary Y. enterocolitica infection in mice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Autenrieth IB; Tingle A, Reske-Kunz A, Heesemann J (1992) T lymphocytes mediate protection against Yersinia enterocolitica in mice: characterization of murine T-cell clones specific for Y. enterocolitica. Infect Immun 60:1140–1149

    Google Scholar 

  2. Bancroft GJ, Schreiber RD, Bosma GC, Bosma MJ, Unanue ER (1987) A T cell-independent mechanism of macrophage activation by interferon-gamma. J Immunol 139:1104–1107

    Google Scholar 

  3. Bancroft GJ, Sheehan KC, Schreiber RD, Unanue ER (1989) Tumor necrosis factor is involved in the T cell-independent pathway of macrophage activation in scid mice. J Immunol 143:127–130

    Google Scholar 

  4. Bermudez LE, Young LS (1988) Tumor necrosis factor, alone or in combination with IL-2, but not IFN-gamma, is associated with macrophage killing of Mycobacterium avium complex. J Immunol 140:3006–3013

    Google Scholar 

  5. Denis M (1991) Modulation of Mycobacterium lepraemurium growth in murine macrophages: beneficial effect of tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor. Infect Immun 59:705–707

    Google Scholar 

  6. Dunn PL, North RJ (1991) Early gamma interferon production by natural killer cells is important in defense against murine listeriosis. Infect Immun 59:2892–2900

    Google Scholar 

  7. Hanski C, Kutschka U, Schmoranzer HP, Naumann M, Stallmach A, Hahn H, Menge H, Riecken EO (1989) Immunohistochemical and electron microscopic study of interaction of Yersinia enterocolitica serotype 08 with intestinal mucosa during experimental enteritis. Infect Immun 57:673–678

    Google Scholar 

  8. Havell EA (1987) Production of tumor necrosis factor during murine listeriosis. J Immunol 139:4225–5231

    Google Scholar 

  9. Heesemann J, Lauf R (1983) Construction of a mobilizable Yersinia enterocolitica virulence plasmid. J Bacteriol 155:761–767

    Google Scholar 

  10. Kagaya K, Watanabe K, Fukazawa Y (1989) Capacity of recombinant gamma Interferon to activate macrophages for Salmonella-killing activity. Infect Immun 57:609–615

    Google Scholar 

  11. Leist TP, Eppler M, Zinkernagel RM (1989) Enhanced virus replication and inhibition of lymphocytic choriomeningitis virus disease in anti-gamma interferon-treated mice. J Virol 63:2813–2819

    Google Scholar 

  12. Lian CJ, Hwang WS, Pai CH (1987) Plasmid-mediated resistance to phagocytosis in Yersinia enterocolitica. Infect Immun 55:1176–1183

    Google Scholar 

  13. Mannel DN, Moore RN, Mergenhagen SE (1980) Macrophages as a sourc eof tumoricidal activity (tumor-necrotizing factor). Infect Immun 30:523–530

    Google Scholar 

  14. Mastroeni P, Arena A, Costa GB, Liberto M, Bonina L, Hormaeche CE (1992) Serum TNFαa in mouse typhoid and enhancement of a salmonella infection by anti-TNF-α antibodies. Microb Pathogen 11:33–38

    Google Scholar 

  15. Muotiala A, Makela PH (1990) The role of IFN-gamma in murine Salmonella typhimurium infection. Microb Pathogen 8:135–141

    Google Scholar 

  16. Nakane A, Minagawa T, Kato K (1988) Endogenous tumor necrosis factor (cachectin) is essential to host resistance against Listeria monocytogenes infection. Infect Immun 56:2563–2569

    Google Scholar 

  17. Nakane A, Numata A, Chen Y, Minagawa T (1991) Endogenous gamma interferon-independent host resistance against Listeria monocytogenes infection in CD4 T cell- and asialo GM1 cell-depleted mice. Infect Immun 59:3439–3445

    Google Scholar 

  18. Nakane A, Numata A, Minagawa T (1992) Endogenous tumor necrosis factor, interleukin-6, and gamma interferon levels during Listeria monocytogenes infection in mice. Infect Immun 60:523–528

    Google Scholar 

  19. Nathan CF, Murray HW, Wiebe ME, Rubin BY (1983) Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med 158:670–689

    Google Scholar 

  20. Nauciel C, Espinasse-Maes F (1992) Role of gamma interferon and tumor necrosis factor alpha in resistance to Salmonella typhimurium infection. Infect Immun 60:450–454

    Google Scholar 

  21. Ramarathinam L, Shaban RA, Niesel DW, Klimpel GR (1992) Interferon gamma (IFN-γ) production by gut-associated lymphoid tissue and spleen following oral Salmonella typhimurium challenge. Microb Pathogen 11:347–356

    Google Scholar 

  22. Simonet M, Richard S, Berche P (1990) Electron microscopic evidence for in vivo extracellular localization of Yersinia pseudotuberculosis harboring the pYV plasmid. Infect Immun 58:841–845

    Google Scholar 

  23. Theodos CM, Povinelli L, Molina R, Sherry B, Titus RG (1991) Role of tumor necrosis factor in macrophage leishmanicidal activity in vitro and resistance to cutaneous leishmaniasis in vivo. Infect Immun 59:2839–2842

    Google Scholar 

  24. Tite JP, Dougan G, Chatfield SN (1992) The involvement of tumor necrosis factor in immunity to Salmonella infection. J Immunol 147:3161–3164

    Google Scholar 

  25. Wherry JC, Schreiber RD, Unanue ER (1991) Regulation of gamma interferon production by natural killer cells in scid mice: roles of tumor necrosis factor and bacterial stimuli. Infect Immun 59:1709–1715

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Autenrieth, I.B., Heesemann, J. In vivo neutralization of tumor necrosis factor-alpha and interferon-gamma abrogates resistance to Yersinia enterocolitica infection in mice. Med Microbiol Immunol 181, 333–338 (1992). https://doi.org/10.1007/BF00191545

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00191545

Keywords

Navigation