Cutting edge: distinct Toll-like receptor 2 activators selectively induce different classes of mediator production from human mast cells.
Mast cells play a critical role in host defense against bacterial infection. Murine mast cells produce cytokines in response to bacterial peptidoglycan and LPS via Toll-like receptor (TLR) TLR2- and TLR4-dependent mechanisms. The expression of TLRs by human mast cells and responses to known TLR activators was examined. Human mast cells expressed mRNA for TLR1, TLR2, and TLR6 but not TLR4. Bacterial peptidoglycan and yeast zymosan were potent inducers of GM-CSF and IL-1beta and also induced substantial short-term cysteinyl leukotriene generation. In contrast, a synthetic triacylated lipopeptide induced short-term degranulation but failed to induce cysteinyl leukotriene production. The TLR4 activator Escherichia coli LPS did not induce a GM-CSF, IL-1beta leukotriene, or degranulation response. These data demonstrate highly selective production of different classes of mast cell mediators in response to distinct TLR activators of potential importance to the host response to bacterial or fungal pathogens.
McCurdy
Jeffrey D
JD
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, B3H 4H7 Canada.
Olynych
Timothy J
TJ
Maher
Lauren H
LH
Marshall
Jean S
JS
D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis* / Q000145:classification; D029721:Drosophila Proteins; D004926:Escherichia coli / Q000276:immunology; D006801:Humans; D015289:Leukotrienes / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008074:Lipoproteins / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D010457:Peptidoglycan / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000276:immunology; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors; D014407:Tumor Cells, Cultured; D015054:Zymosan / Q000494:pharmacology; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D016207:Cytokines; D029721:Drosophila Proteins; D015289:Leukotrienes; D008070:Lipopolysaccharides; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D010457:Peptidoglycan; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495368:TLR6 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors; C112381:cysteinyl-leukotriene; C069172:2,3-bis(palmitoyloxy)-2-propyl-1-palmitoylcysteine; D015054:Zymosan; D001619:beta-N-Acetylhexosaminidases; D003545:Cysteine