Enhancement of Mycobacterium tuberculosis-induced tumor necrosis factor alpha production from primary human monocytes by an activated T-cell membrane-mediated mechanism.
Mycobacterium tuberculosis alone induces small, donor-variable amounts of tumor necrosis factor alpha (TNF-alpha) from primary human monocytes in vitro. However, TNF-alpha release is increased 5- to 500-fold when fixed activated T cells (FAT) or their isolated, unfixed membranes are added to this system. This FAT-induced synergy was at least as potent as that induced by gamma interferon (IFN-gamma) at 100 U/ml. FAT-enhanced TNF-alpha production is at least in part transcriptionally mediated, as reflected by quantitative changes in TNF-alpha mRNA between 2 and 6 h poststimulation. Unlike IFN-gamma-cocultured cells, FAT-treated monocytes appeared not to have enhanced TNF-alpha message stability, suggesting that de novo transcription may be involved in this effect. Furthermore, M. tuberculosis alone induced only minimal DNA binding of monocyte NF-kappaB, but cells treated with M. tuberculosis and FAT potentiated NF-kappaB activity more effectively. It is therefore possible that one mechanism by which FAT synergize with M. tuberculosis to stimulate TNF-alpha production is via NF-kappaB-enhanced transcription. These data strongly suggest that in the interaction of cells involved in the immune response to M. tuberculosis, T-cell stimulation of monocyte TNF-alpha production involves a surface membrane interaction(s) as well as soluble mediators.
Warwick-Davies
J
J
Department of Infectious Diseases, St. George's Hospital Medical School, London, United Kingdom. jan.davies@lshtm.ac.uk
Watson
A J
AJ
Griffin
G E
GE
Krishna
S
S
Shattock
R J
RJ
D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D005404:Fixatives / Q000494:pharmacology; D005557:Formaldehyde / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D011108:Polymers / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D005404:Fixatives; D016328:NF-kappa B; D011108:Polymers; D014409:Tumor Necrosis Factor-alpha; D005557:Formaldehyde; D007371:Interferon-gamma; C003043:paraform