title: Murine mast cells secrete a unique profile of cytokines and prostaglandins in response to distinct TLR2 ligands.
abstract: Mast cells (MCs) are important effector cells in host defense against bacteria. In the course of a bacterial infection, MCs can be activated by various mechanisms, i.e. bacterial toxins, endogenously produced infection-associated peptides or via complement receptors, fimbrial adhesion molecules and toll-like receptors (TLRs). While some of these mechanisms are well established, the effects of TLR2 ligand-driven MC activation are far less understood. Here, we show that murine mature connective tissue-type MCs, but not immature bone marrow-derived cultured mast cells, express significant amounts of full length TLR2 on their surface. Activation by various TLR2 ligands only induces the selective release of cytokines in peritoneum-derived cultured mast cells (PCMCs) with preferential secretion of pro-inflammatory cytokines (IL-6 > IL-17 > IFN-gamma TNF > IL-1 > GM-CSF) upon stimulation with lipoteichoic acid (LTA). This response is much lower in PCMCs stimulated with the TLR2/6 agonist macrophage-activating lipopeptide-2 (MALP-2), which most prominently triggers the release of the immunomodulatory cytokine IL-10. Furthermore, only LTA but not MALP-2 induces prostaglandin D2 secretion which is again restricted to the mature MC phenotype. These findings suggest that TLR2 ligand-mediated activation of mature MCs, i.e. tissue-residing cells, which most likely occurs during infection, can selectively raise a potent inflammatory or anti-inflammatory response, depending on TLRs which are engaged.
authors.affiliation: Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité- Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Salima
authors.initials: S
authors.lastname: Mrabet-Dahbi
authors.forename: Martin
authors.initials: M
authors.lastname: Metz
authors.forename: Anne
authors.initials: A
authors.lastname: Dudeck
authors.forename: Torsten
authors.initials: T
authors.lastname: Zuberbier
authors.forename: Marcus
authors.initials: M
authors.lastname: Maurer
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis*; D005434:Flow Cytometry; D008024:Ligands; D055666:Lipopeptides / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D015230:Prostaglandin D2 / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D013682:Teichoic Acids / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis*
chemical_list: D016207:Cytokines; D008024:Ligands; D055666:Lipopeptides; D008070:Lipopolysaccharides; D011453:Prostaglandins; D013682:Teichoic Acids; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; C009900:lipoteichoic acid; C106335:macrophage stimulatory lipopeptide 2; D015230:Prostaglandin D2