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Attenuation of massive cytokine response to the staphylococcal enterotoxin B superantigen by the innate immunomodulatory protein lactoferrin

  1. J. L. Hayworth1,
  2. K. J. Kasper1,
  3. M. Leon-Ponte1,
  4. C. A. Herfst1,
  5. D. Yue1,
  6. W. C. Brintnell1,
  7. D. M. Mazzuca1,
  8. D. E. Heinrichs1,
  9. E. Cairns1,2,
  10. J. Madrenas1,2,3,
  11. D. W. Hoskin5,
  12. J. K. McCormick1,4,
  13. S. M. M. Haeryfar1,4,*

Article first published online: 22 APR 2009

DOI: 10.1111/j.1365-2249.2009.03963.x

Issue

Clinical & Experimental Immunology

Clinical & Experimental Immunology

Volume 157, Issue 1, pages 60–70, July 2009

Additional Information

How to Cite

Hayworth, J. L., Kasper, K. J., Leon-Ponte, M., Herfst, C. A., Yue, D., Brintnell, W. C., Mazzuca, D. M., Heinrichs, D. E., Cairns, E., Madrenas, J., Hoskin, D. W., McCormick, J. K. and Haeryfar, S. M. M. (2009), Attenuation of massive cytokine response to the staphylococcal enterotoxin B superantigen by the innate immunomodulatory protein lactoferrin. Clinical & Experimental Immunology, 157: 60–70. doi: 10.1111/j.1365-2249.2009.03963.x

Author Information

  1. 1

    Departments of Microbiology and Immunology and

  2. 2

    Medicine, and

  3. 3

    Robarts Research Institute, University of Western Ontario,

  4. 4

    Lawson Health Research Institute, London, ON, and

  5. 5

    Departments of Pathology and Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada

*S. M. M. Haeryfar, Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, 1151 Richmond Street, London, ON, Canada N6A 5C1. E-mail: mansour.haeryfar@schulich.uwo.ca

  1. J. L. Hayworth and K. J. Kasper contributed equally to this study.

Publication History

  1. Issue published online: 10 JUN 2009
  2. Article first published online: 22 APR 2009
  3. Accepted for publication 16 April 2009

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Keywords:

  • cytokine;
  • lactoferrin;
  • staphylococcal enterotoxin B;
  • superantigen

Summary

Staphylococcal enterotoxin B (SEB) is a pyrogenic exotoxin and a potent superantigen which causes massive T cell activation and cytokine secretion, leading to profound immunosuppression and morbidity. The inhibition of SEB-induced responses is thus considered a goal in the management of certain types of staphylococcal infections. Lactoferrin (LF) is a multi-functional glycoprotein with both bacteriostatic and bactericidal activities. In addition, LF is known to have potent immunomodulatory properties. Given the anti-microbial and anti-inflammatory properties of this protein, we hypothesized that LF can modulate T cell responses to SEB. Here, we report that bovine LF (bLF) was indeed able to attenuate SEB-induced proliferation, interleukin-2 production and CD25 expression by human leucocyte antigen (HLA)-DR4 transgenic mouse T cells. This inhibition was not due to bLF's iron-binding capacity, and could be mimicked by the bLF-derived peptide lactoferricin. Cytokine secretion by an engineered SEB-responsive human Jurkat T cell line and by peripheral blood mononuclear cells from healthy donors was also inhibited by bLF. These findings reveal a previously unrecognized property of LF in modulation of SEB-triggered immune activation and suggest a therapeutic potential for this naturally occurring protein during toxic shock syndrome.

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