J. L. Hayworth and K. J. Kasper contributed equally to this study.
Attenuation of massive cytokine response to the staphylococcal enterotoxin B superantigen by the innate immunomodulatory protein lactoferrin
Article first published online: 22 APR 2009
© 2009 British Society for Immunology
Clinical & Experimental Immunology
Volume 157, Issue 1, pages 60–70, July 2009
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
- Issue published online: 10 JUN 2009
- Article first published online: 22 APR 2009
- Accepted for publication 16 April 2009
- staphylococcal enterotoxin B;
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.