Toll-like receptor 2 (TLR2) and TLR4 differentially activate human mast cells.
In the present report we have analyzed whether human normal cord blood-derived mast cells (CBMC) could interact with bacterial products, especially lipopolysaccharide (LPS) from Escherichia coli and peptidoglycan (PGN) from Staphylococcus aureus, known as Toll-like receptor (TLR) 4 and TLR2 agonists, respectively. We found that both LPS and PGN induced significant release of not only tumor necrosis factor-alpha (TNF-alpha), but also IL-5, IL-10 and IL-13 by human mast cells (MC). We also established that the stimulation of CBMC with LPS or with PGN is mediated through interactions with TLR4 or with TLR2, respectively. Thus, our data indicate that activation of either TLR2 or TLR4 pathway may lead to a pro-Th2 immune response. However, the release of TNF-alpha induced by LPS, conversely to PGN, required the priming of CBMC by IL-4 and the presence of serum components, in particular soluble CD14. Of interest, stimulation by PGN, but not by LPS, induced release of histamine by human MC. Altogether, these findings provide the first evidence that human MC differentially respond towards bacterial components, and that their responses depend on TLR pathways and reveal human specificities in the pattern of cytokine production.
Varadaradjalou
Sonia
S
CNRS FRE 2444, Faculty of Pharmacy, Paris V University, Paris, France.
Féger
Frédéric
F
Thieblemont
Nathalie
N
Hamouda
Nadine Ben
NB
Pleau
Jean-Marie
JM
Dy
Michel
M
Arock
Michel
M
D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D029721:Drosophila Proteins; D005312:Fetal Blood / Q000166:cytology; D006636:Histamine Release; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D010457:Peptidoglycan / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D013211:Staphylococcus aureus; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D016207:Cytokines; D029721:Drosophila Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D010457:Peptidoglycan; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D015847:Interleukin-4