Attenuation of Massive Cytokine Response to the Staphylococcal Enterotoxin B Superantigen by the Innate Immunomodulatory Protein Lactoferrin

Authors

J. L. Hayworth, University of Western OntarioFollow
K. J. Kasper, University of Western OntarioFollow
M. Leon-Ponte, University of Western Ontario
C. A. Herfst, University of Western Ontario
D. Yue, University of Western Ontario
W. C. Brintnell, University of Western OntarioFollow
D. M. Mazzuca, University of Western OntarioFollow
D. E. Heinrichs, University of Western OntarioFollow
E. Cairns, University of Western OntarioFollow
J. Madrenas, University of Western OntarioFollow
D. W. Hoskin, Dalhousie University
J. K. McCormick, University of Western OntarioFollow
S. M. M. Haeryfar, University of Western OntarioFollow

Document Type

Article

Publication Date

7-1-2009

Journal

Clinical & Experimental Immunology

Volume

157

Issue

1

First Page

60

Last Page

70

Abstract

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.

Notes

Published in: Clinical & Experimental Immunology, Volume 157, Issue 1, Pages 60 - 70. doi: 10.1111/j.1365-2249.2009.03963.x