1887

Abstract

The present study was conducted to determine the extent to which the cytokines tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) are required to protect against primary or secondary murine tularaemia caused by the live vaccine strain of the facultative intracellular bacterium . It is shown that non-immune mice treated with neutralizing monoclonal antibodies (mAbs) against TNF-α and IFN-γ are rendered defenceless against otherwise sublethal intravenous inocula of the bacterium. Treatment with either of the anti-cytokine mAbs resulted in even a very small inoculum of 500 c.f.u. of the pathogen multiplying unrestrictedly in the livers, spleens and lungs of non-immune mice to rapidly reach lethal numbers. By contrast, -immune mice treated with either of the mAbs remained capable of resolving secondary infection with 50-fold larger inocula. However, the need for TNF-α and IFN-γ for controlling secondary tularaemia became critical when challenge inocula exceeded 10 c.f.u. Overall, the results imply that different defence mechanisms operate to control primary versus secondary murine tularaemia. Additionally, they show that the need for TNF-α and IFN-γ to combat secondary infection depends on the size of the challenge inoculum.

Loading

Article metrics loading...

/content/journal/micro/10.1099/13500872-142-6-1369
1996-06-01
2022-01-24
Loading full text...

Full text loading...

/deliver/fulltext/micro/142/6/mic-142-6-1369.html?itemId=/content/journal/micro/10.1099/13500872-142-6-1369&mimeType=html&fmt=ahah

References

  1. Anthony L.S.D., Burke R.D., Nano F.E. Growth of Francisella spp in rodent macrophages. Infect Immun 1991; 59:3291–3296
    [Google Scholar]
  2. Burke D.S. Immunization against tularemia: analysis of the effectiveness of live Francisella tularensis vaccine on prevention of laboratory-acquired tularemia. J Infect Dis 1977; 135:55–60
    [Google Scholar]
  3. Conlan J.W., North R.J. Early pathogenesis of infection in the liver with the facultative intracellular bacteria Listeria monocytogenes, Francisella tularensis, and Salmonella typhimurium involves lysis of infected hepatocytes by leukocytes. Infect Immun 1992; 60:5164–5171
    [Google Scholar]
  4. Conlan J.W., Sjstedt A., North R.J. CD4+ and CD8+ T cell-dependent and -independent host defense mechanisms can operate to control and resolve primary and secondary Francisella tularensis strain LVS infection in mice. Infect Immun 1994; 62:5603–5607
    [Google Scholar]
  5. Dean C.J., Styles J.M., Gyure L., Peppard J.V., Hobbs S.D.M., Jackson E.C., Hall J.G. The production of hybridomas from the gut-associated lymphoid tissue of rats. I. Mesenteric nodes as a source of IgG-producing cells. Clin Exp Immunol 1984; 57:358–364
    [Google Scholar]
  6. Eigelsbach H.T., Downs C.M. Prophylactic effectiveness of live and killed tularemia vaccine. I. Production of vaccine and evaluation in the white mouse and guinea pig. J Immunol 1961; 87:415–425
    [Google Scholar]
  7. Elkins K.L., Leiby D.A., Winegar R.K., Nacy C.A., Fortier A.H. Rapid generation of specific protective immunity to Francisella tularensis. Infect Immun 1992; 60:4571–4577
    [Google Scholar]
  8. Elkins K.L., Rhinehart-Jones T.R., Nacy C.A., Winegar R.K., Fortier A.H. T-cell-independent resistance to infection and generation of immunity to Francisella tularensis. Infect Immun 1993; 61:823–829
    [Google Scholar]
  9. Fortier A.H., Slayter M.V., Ziemba R., Meltzer M.S., Nacy C.A. Live vaccine strain of Francisella tularensis: infection and immunity in mice. Infect Immun 1991; 59:2922–2928
    [Google Scholar]
  10. Fortier A.H., Polsinelli T., Green S.J., Nacy C.A. Activation of macrophages for destruction of Francisella tularensis: identification of cytokines, effector cells, and effector molecules. Infect Immun 1992; 60:817–825
    [Google Scholar]
  11. Havell E.A. Evidence that tumor necrosis factor has an important role in antibacterial resistance. J Immunol 1989; 143:2894–2899
    [Google Scholar]
  12. Leiby D.A., Fortier A.H., Crawford R.M., Schreiber R.D., Nacy C.A. In vivo modulation of the murine immune response to Francisella tularensis strain LVS by administration of anticytokine antibodies. Infect Immun 1992; 60:84–89
    [Google Scholar]
  13. Mackaness G.B. The immunological basis of acquired cellular resistance. J Exp Med 1964; 120:105–124
    [Google Scholar]
  14. Rhinehart-Jones T.R., Fortier A.H., Elkins K.L. Transfer of immunity against lethal murine Francisella infection by specific antibody depends on host gamma interferon and T cells. Infect Immun 1994; 62:3129–3137
    [Google Scholar]
  15. Sjstedt A., Conlan J.W., North R.J. Neutrophils are critical for host defense against primary infection with the facultative intracellular bacterium Francisella tularensis in mice and participate in defense against reinfection. Infect Immun 1994; 62:2779–2783
    [Google Scholar]
  16. Spitalny G.L., Havell E.A. Monoclonal murine gamma interferon inhibits lymphokine-induced antiviral and macrophage tumoricidal activities. J Exp Med 1984; 159:1560–1565
    [Google Scholar]
  17. Tarnvik A. Nature of protective immunity to Francisella tularensis. Rev Infect Dis 1989; 11:440–451
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/13500872-142-6-1369
Loading
/content/journal/micro/10.1099/13500872-142-6-1369
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error