Cutting edge: bradykinin induces IL-12 production by dendritic cells: a danger signal that drives Th1 polarization.
Dendritic cells play a major role in the induction of both innate and acquired immune responses against pathogenic invaders. These cells are also able to sense endogenous activation signals liberated by injured tissues even in the absence of infection. In the present work, we demonstrate that kinins mobilize dendritic cells to produce IL-12 through activation of the B(2) bradykinin receptor subtype and that bradykinin-induced IL-12 responses are tightly regulated both by angiotensin-converting enzyme, a kinin-degrading peptidase, and by endogenous IL-10. Using a mouse model of allergic inflammation, we further show that addition of bradykinin to OVA during immunization results in decreased eosinophil infiltration on Ag challenge. The latter effect was demonstrated to be due to IL-12-driven skewing of Ag-specific T cell responses to a type 1 cytokine profile. Our data thus indicate that kinin peptides can serve as danger signals that trigger dendritic cells to produce IL-12 through activation of B(2) bradykinin receptors.
Aliberti
Julio
J
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA. jalberti@niaid.nih.gov
Viola
João P B
JP
Vieira-de-Abreu
Adriana
A
Bozza
Patricia T
PT
Sher
Alan
A
Scharfstein
Julio
J
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics; D007274:Injections, Intraperitoneal; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000502:physiology; D007609:Kallidin / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010998:Pleurisy / Q000276:immunology / Q000473:pathology; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000172:deficiency / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D000276:Adjuvants, Immunologic; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D018664:Interleukin-12; D007609:Kallidin; D010047:Ovalbumin; D001920:Bradykinin