title: Mast cells have a pivotal role in TNF-independent lymph node hypertrophy and the mobilization of Langerhans cells in response to bacterial peptidoglycan.
abstract: Peptidoglycan (PGN) from Gram-positive bacteria, activates multiple immune effector cells. PGN-induced lymph node (LN) hypertrophy and dendritic cell mobilization in vivo were investigated following PGN injection into the skin. Both LN activation and the migration of Langerhans cells (LCs) to draining LNs were dependent on the presence of mast cells as demonstrated using mast cell deficient W/W(v) mice. However, these responses did not require TLR2, TLR4, or MYD88. TNF-deficient mice exhibited normal increases in LN cellularity but significantly reduced LC migration. In contrast, responses to IgE-mediated mast cell activation were highly TNF dependent. Complement component C3-deficient mice showed decreased LN hypertrophy and abrogated LC migration in response to PGN. These data demonstrate a critical role for mast cells and complement in LN responses to PGN and illustrate a novel TNF-independent mechanism whereby mast cells participate in the initiation of immunity.
authors.affiliation: Dalhousie Inflammation Group, Department of Pathology and Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Dunia M
authors.initials: DM
authors.lastname: Jawdat
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Rowden
authors.forename: Jean S
authors.initials: JS
authors.lastname: Marshall
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D003176:Complement C3 / Q000502:physiology; D006984:Hypertrophy; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D037181:Lectins, C-Type / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D037241:Mannose-Binding Lectins / Q000096:biosynthesis; D008407:Mast Cells / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D053594:Myeloid Differentiation Factor 88; D010457:Peptidoglycan / Q000276:immunology*; D011969:Receptors, Histamine H1 / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000502:physiology; D013211:Staphylococcus aureus / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000954:Antigens, Surface; C498497:Cd207 protein, mouse; D003176:Complement C3; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D010457:Peptidoglycan; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha