Journal Article

Role and regulation of IL-12 in the <i>in vivo</i> response to staphylococcal enterotoxin B

Eric Muraille, Bernard Pajak, Jacques Urbain, Muriel Moser and Oberdan Leo

in International Immunology

Published on behalf of Japanese Society for Immunology

Volume 11, issue 9, pages 1403-1410
Published in print September 1999 | ISSN: 0953-8178
Published online September 1999 | e-ISSN: 1460-2377 | DOI: http://dx.doi.org/10.1093/intimm/11.9.1403
Role and regulation of IL-12 in the in vivo response to staphylococcal enterotoxin B

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Injection of a staphylococcal superantigen (SAg) such as staphylococcal enterotoxin B (SEB) in adult mice results in cytokine production and cell proliferation which can lead to septic shock. The aim of the present work was to identify the cytokines and co-stimulatory molecules regulating the in vivo systemic release of IFN-γ, a cytokine known to play an important role in the pathophysiology associated with bacterial infections. We demonstrate in this study that (i) in contrast to lipopolysaccharide (LPS), SEB administration induces high levels of the p70, bioactive form, of IL-12; (ii) IL-12 production in response to SEB requires both CD40-dependent signals and IFN-γ secretion; (iii) the early systemic release of IFN-γ (3 h post-treatment) in response to SEB is IL-12 independent, while the sustained, late response (6–9 h post-treatment) requires endogenous IL-12 production; (iv) IL-12 produced during the primary SEB response (day 0) is responsible for priming cells in vivo to high IFN-γ production upon secondary challenge (day 2); (v) the priming effect of IL-12 is TCR unrelated, as SEB-primed animals secrete high levels of IFN-γ in response to both staphylococcal enterotoxin A and LPS administered 48 h later. The ability of bacterial SAg to induce septic shock and to modulate the immune response to unrelated antigens may therefore be related to their unique capacity to induce systemic IL-12 production in vivo. These observations also help to explain why SEB-primed animals, known to express an anergic phenotype 48 h post-treatment (as judged by defective IL-2 production and proliferation), nevertheless display an increased capacity to secrete the inflammatory cytokine IFN-γ.

Keywords: cytokines; inflammatory responses; in vivo responses; lipopolysaccharide; superantigens; APC antigen-presenting cell; CD40L CD40 ligand; LPS lipopolysaccharide; SAg superantigen; SEA staphylococcal enterotoxin A; SEB staphylococcal enterotoxin B

Journal Article.  5762 words.  Illustrated.

Subjects: Immunology ; Biological Sciences

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