Microbiology & Immunology Publications

Title

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

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