Cutting Edge: Bradykinin Induces IL-12 Production by Dendritic Cells: A Danger Signal That Drives Th1 Polarization

• Published in: The Journal of immunology (1950) Vol. 170; no. 11; pp. 5349 - 5353
• Main Authors: Aliberti, Julio, Viola, Joao P. B, Vieira-de-Abreu, Adriana, Bozza, Patricia T, Sher, Alan, Scharfstein, Julio
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01-06-2003
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - pharmacology; Adjuvants, Immunologic - physiology; Animals; Bradykinin - administration & dosage; Bradykinin - physiology; Cell Movement - drug effects; Cell Movement - immunology; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - metabolism; Disease Models, Animal; Eosinophils - drug effects; Eosinophils - pathology; Female; Immunity, Innate - drug effects; Immunity, Innate - genetics; Injections, Intraperitoneal; Interleukin-12 - biosynthesis; Interleukin-12 - physiology; Kallidin - administration & dosage; Kallidin - pharmacology; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin - administration & dosage; Ovalbumin - immunology; Pleurisy - immunology; Pleurisy - pathology; Receptor, Bradykinin B2; Receptors, Bradykinin - deficiency; Receptors, Bradykinin - genetics; Spleen - cytology; Spleen - drug effects; Spleen - immunology; Spleen - metabolism; Th1 Cells - drug effects; Th1 Cells - immunology; Th1 Cells - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.170.11.5349

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.