Bradykinin B2 Receptors of dendritic cells, acting as sensors of kinins proteolytically released by Trypanosoma cruzi, are critical for the development of protective type-1 responses.
Although the concept that dendritic cells (DCs) recognize pathogens through the engagement of Toll-like receptors is widely accepted, we recently suggested that immature DCs might sense kinin-releasing strains of Trypanosoma cruzi through the triggering of G-protein-coupled bradykinin B2 receptors (...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2007-11-01
|
Series: | PLoS Pathogens |
Online Access: | http://europepmc.org/articles/PMC2098834?pdf=render |
id |
doaj-2575dc313b634774b41fff5c93d6b73c |
---|---|
record_format |
Article |
spelling |
doaj-2575dc313b634774b41fff5c93d6b73c2020-11-24T21:20:03ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742007-11-01311e18510.1371/journal.ppat.0030185Bradykinin B2 Receptors of dendritic cells, acting as sensors of kinins proteolytically released by Trypanosoma cruzi, are critical for the development of protective type-1 responses.Ana Carolina MonteiroVerônica SchmitzAlexandre MorrotLuciana Barros de ArrudaFnu NagajyothiAlessandra GranatoJoão B PesqueroWerner Müller-EsterlHerbert B TanowitzJulio ScharfsteinAlthough the concept that dendritic cells (DCs) recognize pathogens through the engagement of Toll-like receptors is widely accepted, we recently suggested that immature DCs might sense kinin-releasing strains of Trypanosoma cruzi through the triggering of G-protein-coupled bradykinin B2 receptors (B2R). Here we report that C57BL/6.B2R-/- mice infected intraperitoneally with T. cruzi display higher parasitemia and mortality rates as compared to B2R+/+ mice. qRT-PCR revealed a 5-fold increase in T. cruzi DNA (14 d post-infection [p.i.]) in B2R-/- heart, while spleen parasitism was negligible in both mice strains. Analysis of recall responses (14 d p.i.) showed high and comparable frequencies of IFN-gamma-producing CD4+ and CD8+ T cells in the spleen of B2R-/- and wild-type mice. However, production of IFN-gamma by effector T cells isolated from B2R-/- heart was significantly reduced as compared with wild-type mice. As the infection continued, wild-type mice presented IFN-gamma-producing (CD4+CD44+ and CD8+CD44+) T cells both in the spleen and heart while B2R-/- mice showed negligible frequencies of such activated T cells. Furthermore, the collapse of type-1 immune responses in B2R-/- mice was linked to upregulated secretion of IL-17 and TNF-alpha by antigen-responsive CD4+ T cells. In vitro analysis of tissue culture trypomastigote interaction with splenic CD11c+ DCs indicated that DC maturation (IL-12, CD40, and CD86) is controlled by the kinin/B2R pathway. Further, systemic injection of trypomastigotes induced IL-12 production by CD11c+ DCs isolated from B2R+/+ spleen, but not by DCs from B2R-/- mice. Notably, adoptive transfer of B2R+/+ CD11c+ DCs (intravenously) into B2R-/- mice rendered them resistant to acute challenge, rescued development of type-1 immunity, and repressed TH17 responses. Collectively, our results demonstrate that activation of B2R, a DC sensor of endogenous maturation signals, is critically required for development of acquired resistance to T. cruzi infection.http://europepmc.org/articles/PMC2098834?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ana Carolina Monteiro Verônica Schmitz Alexandre Morrot Luciana Barros de Arruda Fnu Nagajyothi Alessandra Granato João B Pesquero Werner Müller-Esterl Herbert B Tanowitz Julio Scharfstein |
spellingShingle |
Ana Carolina Monteiro Verônica Schmitz Alexandre Morrot Luciana Barros de Arruda Fnu Nagajyothi Alessandra Granato João B Pesquero Werner Müller-Esterl Herbert B Tanowitz Julio Scharfstein Bradykinin B2 Receptors of dendritic cells, acting as sensors of kinins proteolytically released by Trypanosoma cruzi, are critical for the development of protective type-1 responses. PLoS Pathogens |
author_facet |
Ana Carolina Monteiro Verônica Schmitz Alexandre Morrot Luciana Barros de Arruda Fnu Nagajyothi Alessandra Granato João B Pesquero Werner Müller-Esterl Herbert B Tanowitz Julio Scharfstein |
author_sort |
Ana Carolina Monteiro |
title |
Bradykinin B2 Receptors of dendritic cells, acting as sensors of kinins proteolytically released by Trypanosoma cruzi, are critical for the development of protective type-1 responses. |
title_short |
Bradykinin B2 Receptors of dendritic cells, acting as sensors of kinins proteolytically released by Trypanosoma cruzi, are critical for the development of protective type-1 responses. |
title_full |
Bradykinin B2 Receptors of dendritic cells, acting as sensors of kinins proteolytically released by Trypanosoma cruzi, are critical for the development of protective type-1 responses. |
title_fullStr |
Bradykinin B2 Receptors of dendritic cells, acting as sensors of kinins proteolytically released by Trypanosoma cruzi, are critical for the development of protective type-1 responses. |
title_full_unstemmed |
Bradykinin B2 Receptors of dendritic cells, acting as sensors of kinins proteolytically released by Trypanosoma cruzi, are critical for the development of protective type-1 responses. |
title_sort |
bradykinin b2 receptors of dendritic cells, acting as sensors of kinins proteolytically released by trypanosoma cruzi, are critical for the development of protective type-1 responses. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2007-11-01 |
description |
Although the concept that dendritic cells (DCs) recognize pathogens through the engagement of Toll-like receptors is widely accepted, we recently suggested that immature DCs might sense kinin-releasing strains of Trypanosoma cruzi through the triggering of G-protein-coupled bradykinin B2 receptors (B2R). Here we report that C57BL/6.B2R-/- mice infected intraperitoneally with T. cruzi display higher parasitemia and mortality rates as compared to B2R+/+ mice. qRT-PCR revealed a 5-fold increase in T. cruzi DNA (14 d post-infection [p.i.]) in B2R-/- heart, while spleen parasitism was negligible in both mice strains. Analysis of recall responses (14 d p.i.) showed high and comparable frequencies of IFN-gamma-producing CD4+ and CD8+ T cells in the spleen of B2R-/- and wild-type mice. However, production of IFN-gamma by effector T cells isolated from B2R-/- heart was significantly reduced as compared with wild-type mice. As the infection continued, wild-type mice presented IFN-gamma-producing (CD4+CD44+ and CD8+CD44+) T cells both in the spleen and heart while B2R-/- mice showed negligible frequencies of such activated T cells. Furthermore, the collapse of type-1 immune responses in B2R-/- mice was linked to upregulated secretion of IL-17 and TNF-alpha by antigen-responsive CD4+ T cells. In vitro analysis of tissue culture trypomastigote interaction with splenic CD11c+ DCs indicated that DC maturation (IL-12, CD40, and CD86) is controlled by the kinin/B2R pathway. Further, systemic injection of trypomastigotes induced IL-12 production by CD11c+ DCs isolated from B2R+/+ spleen, but not by DCs from B2R-/- mice. Notably, adoptive transfer of B2R+/+ CD11c+ DCs (intravenously) into B2R-/- mice rendered them resistant to acute challenge, rescued development of type-1 immunity, and repressed TH17 responses. Collectively, our results demonstrate that activation of B2R, a DC sensor of endogenous maturation signals, is critically required for development of acquired resistance to T. cruzi infection. |
url |
http://europepmc.org/articles/PMC2098834?pdf=render |
work_keys_str_mv |
AT anacarolinamonteiro bradykininb2receptorsofdendriticcellsactingassensorsofkininsproteolyticallyreleasedbytrypanosomacruziarecriticalforthedevelopmentofprotectivetype1responses AT veronicaschmitz bradykininb2receptorsofdendriticcellsactingassensorsofkininsproteolyticallyreleasedbytrypanosomacruziarecriticalforthedevelopmentofprotectivetype1responses AT alexandremorrot bradykininb2receptorsofdendriticcellsactingassensorsofkininsproteolyticallyreleasedbytrypanosomacruziarecriticalforthedevelopmentofprotectivetype1responses AT lucianabarrosdearruda bradykininb2receptorsofdendriticcellsactingassensorsofkininsproteolyticallyreleasedbytrypanosomacruziarecriticalforthedevelopmentofprotectivetype1responses AT fnunagajyothi bradykininb2receptorsofdendriticcellsactingassensorsofkininsproteolyticallyreleasedbytrypanosomacruziarecriticalforthedevelopmentofprotectivetype1responses AT alessandragranato bradykininb2receptorsofdendriticcellsactingassensorsofkininsproteolyticallyreleasedbytrypanosomacruziarecriticalforthedevelopmentofprotectivetype1responses AT joaobpesquero bradykininb2receptorsofdendriticcellsactingassensorsofkininsproteolyticallyreleasedbytrypanosomacruziarecriticalforthedevelopmentofprotectivetype1responses AT wernermulleresterl bradykininb2receptorsofdendriticcellsactingassensorsofkininsproteolyticallyreleasedbytrypanosomacruziarecriticalforthedevelopmentofprotectivetype1responses AT herbertbtanowitz bradykininb2receptorsofdendriticcellsactingassensorsofkininsproteolyticallyreleasedbytrypanosomacruziarecriticalforthedevelopmentofprotectivetype1responses AT julioscharfstein bradykininb2receptorsofdendriticcellsactingassensorsofkininsproteolyticallyreleasedbytrypanosomacruziarecriticalforthedevelopmentofprotectivetype1responses |
_version_ |
1726004168860106752 |