SEB-induced signaling in macrophages leads to biphasic TNF-alpha.
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-kappaB 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.
Khan
Aslam Ali
AA
National Centre for Cell Science, Ganeshkhind, Pune, India.
Martin
Sunil
S
Saha
Bhaskar
B
D000818:Animals; D017951:Antigen Presentation; D002478:Cells, Cultured; D004768:Enterotoxins / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C031818:enterotoxin B, staphylococcal; D066246:ErbB Receptors; D048051:p38 Mitogen-Activated Protein Kinases