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SEB‐induced signaling in macrophages leads to biphasic TNF‐α
Author(s) -
Khan Aslam Ali,
Martin Sunil,
Saha Bhaskar
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1007686
Subject(s) - biology , microbiology and biotechnology , major histocompatibility complex , signal transduction , macrophage , tumor necrosis factor alpha , immunology , antigen , biochemistry , in vitro
APCs express MHC‐II molecules. Binding of enterotoxins to MHC‐II generates a signal resulting in the production of TNF‐α that mediates toxic shock syndrome. However, the signaling events that lead to TNF‐α 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‐α‐converting enzyme, epidermal growth factor receptor, p38MAPK, and NF‐κB inducing biphasic TNF‐α production. Paraformaldehyde‐fixed, peptide‐specific T cells also activate MHC‐II signaling and TNF‐α 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.