Mast cells are crucial for early inflammation, migration of Langerhans cells, and CTL responses following topical application of TLR7 ligand in mice.
Until recently, IgE-activated mast cells have been regarded merely as effector cells of adaptive immune responses, involved in allergic reactions and mucosal immunity to parasites. Herein, we report that murine dermal mast cells, activated by local administration of a cream containing the synthetic TLR7 ligand imiquimod, are essential to initiate an early inflammatory reaction. The mast-cell-derived cytokines TNF-alpha and IL-1beta play an important role in this process. Furthermore, TLR7-activated mast cells are also able to promote the emigration of Langerhans cells, which partly depends on the expression of mast-cell-derived IL-1beta. We have previously shown that TLR7 ligation enhances transcutaneous immunization evoked by topical application of vaccine antigens to the skin, a procedure that directly targets skin-resident antigen-presenting cells. Consequently, we now demonstrate here that the capacity to mount a peptide-specific cytotoxic T-lymphocyte response following transcutaneous immunization using imiquimod as adjuvant is severely impaired in mast-cell-deficient mice. Thus, these findings demonstrate the potent versatility of alternatively activated mast cells at the interface of innate and adaptive immunity.
Heib
Valeska
V
Institute for Immunology, University of Mainz, Mainz, Germany.
Becker
Marc
M
Warger
Tobias
T
Rechtsteiner
Gerd
G
Tertilt
Christine
C
Klein
Matthias
M
Bopp
Tobias
T
Taube
Christian
C
Schild
Hansjörg
H
Schmitt
Edgar
E
Stassen
Michael
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000380:Agranulocytosis / Q000276:immunology; D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D000941:Antigens / Q000276:immunology / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology; D000077271:Imiquimod; D007111:Immunity, Cellular / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D007114:Immunization; D007073:Immunoglobulin E / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D007801:Langerhans Cells / Q000276:immunology*; D008024:Ligands; D008407:Mast Cells / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000819:agonists* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000819:agonists* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014612:Vaccines / Q000276:immunology / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D000941:Antigens; D053583:Interleukin-1beta; D008024:Ligands; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D014409:Tumor Necrosis Factor-alpha; D014612:Vaccines; D007073:Immunoglobulin E; D000077271:Imiquimod