| Author | Nascimento, Clarissa R. | |
| Author | Andrade, Daniele | |
| Author | Pinto, Carla Eponina | |
| Author | Serra, Rafaela Rangel | |
| Author | Vellasco, Lucas | |
| Author | Brasil, Guilherme | |
| Author | Ramos Junior, Erivan Schnaider | |
| Author | Mota, Julia Barbalho da | |
| Author | Almeida, Larissa Nogueira | |
| Author | Andrade, Marcus V. | |
| Author | Soeiro, Maria de Nazaré Correia | |
| Author | Juliano, Luiz | |
| Author | Alvarenga, Patrícia Hessab | |
| Author | Oliveira, Ana Carolina | |
| Author | Sicuro, Fernando Lencastre | |
| Author | Carvalho, Antônio C. Campos de | |
| Author | Svensjö, Erik | |
| Author | Scharfstein, Julio | |
| Access date | 2018-02-27T12:52:44Z | |
| Available date | 2018-02-27T12:52:44Z | |
| Document date | 2017 | |
| Citation | NASCIMENTO, Clarissa R. et al. Mast cell coupling to the Kallikrein–Kinin system Fuels intracardiac Parasitism and Worsens heart Pathology in experimental chagas Disease. Frontiers in Immunology, v.8, Article 840, 15p, Aug. 2017. | pt_BR |
| ISSN | 1664-3224 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/24959 | |
| Language | eng | pt_BR |
| Publisher | Frontiers Media | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Doença de Chagas | pt_BR |
| Subject in Portuguese | Trypanosoma cruzi | pt_BR |
| Subject in Portuguese | Bradicinina | pt_BR |
| Subject in Portuguese | Endotelinas | pt_BR |
| Subject in Portuguese | Calicreínas | pt_BR |
| Subject in Portuguese | Mastócitos | pt_BR |
| Title | Mast Cell Coupling to the Kallikrein-Kinin System Fuels Intracardiac Parasitism and Worsens Heart Pathology in Experimental Chagas Disease | pt_BR |
| Type | Article | |
| DOI | 10.3389/fimmu.2017.00840 | |
| Abstract | During the course of Chagas disease, infectious forms ofTrypanosoma cruziare occasionally liberated from parasitized heart cells. Studies performed with tissue culture trypomastigotes (TCTs, Dm28c strain) demonstrated that these parasites evoke neutrophil/CXCR2-dependent microvascular leakage by activating innate sentinel cellsviatoll-like receptor 2 (TLR2). Upon plasma extravasation, proteolytically derived kinins and C5a stimulate immunoprotective Th1 responsesviacross-talk between bradykinin B2 receptors (B2Rs) and C5aR. Awareness that TCTs invade cardiovascular cellsin vitro viainterdependent activation of B2R and endothelin receptors [endothelin A receptor (ETAR)/endothelin B receptor (ETBR)] led us to hypothesize thatT. cruzimight reciprocally benefit from the formation of infection-associated edemaviaactivation of kallikrein-kinin system (KKS). Using intravital microscopy, here we first examined the functional interplay between mast cells (MCs) and the KKS by topically exposing the hamster cheek pouch (HCP) tissues to dextran sulfate (DXS), a potent "contact" activator of the KKS. Surprisingly, although DXS was inert for at least 30 min, a subtle MC-driven leakage resulted in factor XII (FXII)-dependent activation of the KKS, which then amplified inflammationviageneration of bradykinin (BK). Guided by this mechanistic insight, we next exposed TCTs to "leaky" HCP-forged by low dose histamine application-and found that the proinflammatory phenotype of TCTs was boosted by BK generatedviathe MC/KKS pathway. Measurements of footpad edema in MC-deficient mice linked TCT-evoked inflammation to MC degranulation (upstream) and FXII-mediated generation of BK (downstream). We then inoculated TCTs intracardiacally in mice and found a striking decrease of parasite DNA (quantitative polymerase chain reaction; 3 d.p.i.) in the heart of MC-deficient mutant mice. Moreover, the intracardiac parasite load was significantly reduced in WT mice pretreated with (i) cromoglycate (MC stabilizer) (ii) infestin-4, a specific inhibitor of FXIIa (iii) HOE-140 (specific antagonist of B2R), and (iv) bosentan, a non-selective antagonist of ETAR/ETBR. Notably, histopathology of heart tissues from mice pretreated with these G protein-coupled receptors blockers revealed that myocarditis and heart fibrosis (30 d.p.i.) was markedly and redundantly attenuated. Collectively, our study suggests that inflammatory edema propagatedviaactivation of the MC/KKS pathway fuels intracardiac parasitism by generating infection-stimulatory peptides (BK and endothelins) in the edematous heart tissues. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal Fluminense. Instituto de Química. Departamento de Imunobiologia. Niterói, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / University of the Pacific. San Francisco, CA, USA. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. faculdade de Medicina. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Departamento de Clínica Médica. Belo Horizonte, MG, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Affilliation | Universidade Federal de São Paulo. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade do Estado do Rio de Janeiro. Centro Biomédico Rio de Janeiro. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | bradykinin | pt_BR |
| Subject | Chagas Disease | pt_BR |
| Subject | endothelin | pt_BR |
| Subject | G protein-coupled receptors | pt_BR |
| Subject | kallikrein | pt_BR |
| Subject | mast cells | pt_BR |
| Subject | Trypanosoma cruzi | pt_BR |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
