Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/7174
Title: Cooperative Activation of TLR2 and Bradykinin B2 Receptor Is Required for Induction of Type 1 Immunity in a Mouse Model of Subcutaneous Infection byTrypanosoma cruzi
Authors: Monteiro, Ana Carolina
Schmitz, Veronica
Svensjo, Erik
Gazzinelli, Ricardo Tostes
Almeida, Igor Correia de
Todorov, Alex
Arruda, Luciana B. de
Torrecilhas, Ana Claudia Trocoli
Pesquero, João Bosco
Morrot, Alexandre
Bouskela, Eliete
Bonomo, Adriana
Lima, Ana Paula Cabral de Araujo
Esterl, Werner Muller
Scharfstein, Julio
Affilliation: Universidade Federal do Rio de Janeiro. Instituto de Biofisica Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil
Universidade Federal do Rio de Janeiro. Instituto de Biofisica Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil
Universidade Federal do Rio de Janeiro. Instituto de Biofisica Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratorio de Imunopatologia. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Bioquımica e Imunologia. Belo Horizonte, MG, Brazil
University of Texas. Department of Biological Sciences. El Paso, TX, USA
Universidade Federal do Rio de Janeiro. Instituto de Biofisica Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Rio de Janeiro, RJ, Brazil
Universidade de São Paulo. Departamento de Bioquimica. São Paulo, SP, Brazil
Universidade Federal de São Paulo. Departmento de Biofisica. São Paulo, SP, Brazil
Johns Hopkins University. Department of Molecular Microbiology and Immunology. Baltimore, MD
Universidade do Estado do Rio de Janeiro. Laboratorio de Microcirculação. Rio de Janeiro, RJ, Brazil
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Rio de Janeiro, RJ, Brazil
Universidade Federal do Rio de Janeiro. Instituto de Biofisica Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil
University of Frankfurt. Medical School. Institute of Biochemistry II. Frankfurt, Germany
Universidade Federal do Rio de Janeiro. Instituto de Biofisica Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil
Abstract: We have previously reported that exogenous bradykinin activates immature dendritic cells (DCs) via the bradykinin B(2) receptor (B(2)R), thereby stimulating adaptive immunity. In this study, we show that these premises are met in a model of s.c. infection by Trypanosoma cruzi, a protozoan that liberates kinins from kininogens through its major protease, cruzipain. Intensity of B(2)R-dependent paw edema evoked by trypomastigotes correlated with levels of IL-12 produced by CD11c(+) dendritic cells isolated from draining lymph nodes. The IL-12 response induced by endogenously released kinins was vigorously increased in infected mice pretreated with inhibitors of angiotensin converting enzyme (ACE), a kinin-degrading metallopeptidase. Furthermore, these innate stimulatory effects were linked to B(2)R-dependent up-regulation of IFN-gamma production by Ag-specific T cells. Strikingly, the trypomastigotes failed to up-regulate type 1 immunity in TLR2(-/-) mice, irrespective of ACE inhibitor treatment. Analysis of the dynamics of inflammation revealed that TLR2 triggering by glycosylphosphatidylinositol-anchored mucins induces plasma extravasation, thereby favoring peripheral accumulation of kininogens in sites of infection. Further downstream, the parasites generate high levels of innate kinin signals in peripheral tissues through the activity of cruzipain. The demonstration that the deficient type 1 immune responses of TLR2(-/-) mice are rescued upon s.c. injection of exogenous kininogens, along with trypomastigotes, supports the notion that generation of kinin "danger" signals is intensified through cooperative activation of TLR2 and B(2)R. In summary, we have described a s.c. infection model where type 1 immunity is vigorously up-regulated by bradykinin, an innate signal whose levels in peripheral tissues are controlled by an intricate interplay of TLR2, B(2)R, and ACE.
Keywords: Trypanosoma cruzi
Cell Differentiation
Cysteine Endopeptidases/metabolism
Disease Models, Animal
Receptor, Bradykinin B2/genetics
Issue Date: 2006
Publisher: American Association of Immunologists
Citation: MONTEIRO, Ana Carolina et al. Cooperative Activation of TLR2 and Bradykinin B2 Receptor Is Required for Induction of Type 1 Immunity in a Mouse Model of Subcutaneous Infection byTrypanosoma cruzi. J Immunol. 2006 Nov 1;177(9):6325-35
ISSN: 0022-1767
Copyright: restricted access
Appears in Collections:MG - IRR - Artigos de Periódicos

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