Attenuation of massive cytokine response to the staphylococcal enterotoxin B superantigen by the innate immunomodulatory protein lactoferrin.
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.
Hayworth
J L
JL
Department of Microbiology and Immunology, University of Western Ontario, ON, USA.
Kasper
K J
KJ
Leon-Ponte
M
M
Herfst
C A
CA
Yue
D
D
Brintnell
W C
WC
Mazzuca
D M
DM
Heinrichs
D E
DE
Cairns
E
E
Madrenas
J
J
Hoskin
D W
DW
McCormick
J K
JK
Haeryfar
S M M
SM
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001059:Apoproteins / Q000494:pharmacology; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D004768:Enterotoxins / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015804:HLA-DR4 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000032:analysis / Q000096:biosynthesis*; D019169:Jurkat Cells; D007781:Lactoferrin / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012709:Serum Albumin / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014168:Transferrin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001059:Apoproteins; D004768:Enterotoxins; D015804:HLA-DR4 Antigen; D007376:Interleukin-2; D012709:Serum Albumin; D018089:Superantigens; D014168:Transferrin; C028284:apotransferrin; C082171:lactoferricin B; C031818:enterotoxin B, staphylococcal; D007781:Lactoferrin