Mast Cells Have a Pivotal Role in TNF-Independent Lymph Node Hypertrophy and the Mobilization of Langerhans Cells in Response to Bacterial Peptidoglycan

• Published in: Journal of Immunology 2006-08, Vol.177 (3), p.1755-1762
• Main Authors: Jawdat, Dunia M, Rowden, Geoffrey, Marshall, Jean S
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - deficiency; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - physiology; Animals; Antigens, Surface - biosynthesis; Bacteria; Cell Differentiation - immunology; Cell Movement - genetics; Cell Movement - immunology; Complement C3 - physiology; Hypertrophy; Langerhans Cells - immunology; Langerhans Cells - metabolism; Langerhans Cells - microbiology; Langerhans Cells - pathology; Lectins, C-Type - biosynthesis; Lymph Nodes - immunology; Lymph Nodes - metabolism; Lymph Nodes - microbiology; Lymph Nodes - pathology; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Mannose-Binding Lectins - biosynthesis; Mast Cells - immunology; Mast Cells - microbiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Mutant Strains; Myeloid Differentiation Factor 88; Peptidoglycan - immunology; Receptors, Histamine H1 - physiology; Receptors, Histamine H2 - physiology; Staphylococcus aureus - immunology; Toll-Like Receptor 2 - deficiency; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - physiology; Toll-Like Receptor 4 - deficiency; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - physiology; Tumor Necrosis Factor-alpha - deficiency; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - physiology
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.177.3.1755

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.