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Originally published online as doi:10.1189/jlb.1007686 on March 25, 2008

Published online before print March 25, 2008
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(Journal of Leukocyte Biology. 2008;83:1363-1369.)
© 2008 by Society for Leukocyte Biology

SEB-induced signaling in macrophages leads to biphasic TNF-{alpha}

Aslam Ali Khan, Sunil Martin and Bhaskar Saha1

National Centre for Cell Science, Ganeshkhind, Pune, India

1Correspondence: National Centre for Cell Science, Ganeshkhind, Pune 411007, India. E-mail: sahab{at}nccs.res.in

ABSTRACT

APCs express MHC-II molecules. Binding of enterotoxins to MHC-II generates a signal resulting in the production of TNF-{alpha} that mediates toxic shock syndrome. However, the signaling events that lead to TNF-{alpha} production in macrophages are not well understood. We, for the first time, demonstrate that binding of staphylococcal enterotoxin B to MHC-II results in activation of TNF-{alpha}-converting enzyme, epidermal growth factor receptor, p38MAPK, and NF-{kappa}B inducing biphasic TNF-{alpha} production. Paraformaldehyde-fixed, peptide-specific T cells also activate MHC-II signaling and TNF-{alpha} induction in peptide-pulsed macrophages. Our results reveal a novel MHC-II signaling and bidirectional macrophage-T cell interaction regulating macrophage functions. This knowledge may help to develop novel, macrophage-directed, therapeutic strategies.

Key Words: MHC class-II signaling • staphylococcal enterotoxin B • superantigen • APC-T cell interaction






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