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Bordetella Adenylate Cyclase Toxin Differentially Modulates Toll-Like Receptor-Stimulated Activation, Migration and T Cell Stimulatory Capacity of Dendritic Cells

Adenylate cyclase toxin (CyaA) is a key virulence factor of the whooping cough agent Bordetella pertussis. The toxin targets CD11b-expressing phagocytes and delivers into their cytosol an adenylyl cyclase (AC) enzyme that subverts cellular signaling by increasing cAMP levels. In the present study, w...

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Autores principales: Adkins, Irena, Kamanova, Jana, Kocourkova, Aneta, Svedova, Martina, Tomala, Jakub, Janova, Hana, Masin, Jiri, Chladkova, Barbora, Bumba, Ladislav, Kovar, Marek, Ross, Padraig J., Tuckova, Ludmila, Spisek, Radek, Mills, Kingston H. G., Sebo, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4118975/
https://www.ncbi.nlm.nih.gov/pubmed/25084094
http://dx.doi.org/10.1371/journal.pone.0104064
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author Adkins, Irena
Kamanova, Jana
Kocourkova, Aneta
Svedova, Martina
Tomala, Jakub
Janova, Hana
Masin, Jiri
Chladkova, Barbora
Bumba, Ladislav
Kovar, Marek
Ross, Padraig J.
Tuckova, Ludmila
Spisek, Radek
Mills, Kingston H. G.
Sebo, Peter
author_facet Adkins, Irena
Kamanova, Jana
Kocourkova, Aneta
Svedova, Martina
Tomala, Jakub
Janova, Hana
Masin, Jiri
Chladkova, Barbora
Bumba, Ladislav
Kovar, Marek
Ross, Padraig J.
Tuckova, Ludmila
Spisek, Radek
Mills, Kingston H. G.
Sebo, Peter
author_sort Adkins, Irena
collection PubMed
description Adenylate cyclase toxin (CyaA) is a key virulence factor of the whooping cough agent Bordetella pertussis. The toxin targets CD11b-expressing phagocytes and delivers into their cytosol an adenylyl cyclase (AC) enzyme that subverts cellular signaling by increasing cAMP levels. In the present study, we analyzed the modulatory effects of CyaA on adhesive, migratory and antigen presenting properties of Toll-like receptor (TLR)-activated murine and human dendritic cells (DCs). cAMP signaling of CyaA enhanced TLR-induced dissolution of cell adhesive contacts and migration of DCs towards the lymph node-homing chemokines CCL19 and CCL21 in vitro. Moreover, we examined in detail the capacity of toxin-treated DCs to induce CD4(+) and CD8(+) T cell responses. Exposure to CyaA decreased the capacity of LPS-stimulated DCs to present soluble protein antigen to CD4(+) T cells independently of modulation of co-stimulatory molecules and cytokine production, and enhanced their capacity to promote CD4(+)CD25(+)Foxp3(+) T regulatory cells in vitro. In addition, CyaA decreased the capacity of LPS-stimulated DCs to induce CD8(+) T cell proliferation and limited the induction of IFN-γ producing CD8(+) T cells while enhancing IL-10 and IL-17-production. These results indicate that through activation of cAMP signaling, the CyaA may be mobilizing DCs impaired in T cell stimulatory capacity and arrival of such DCs into draining lymph nodes may than contribute to delay and subversion of host immune responses during B. pertussis infection.
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spelling pubmed-41189752014-08-04 Bordetella Adenylate Cyclase Toxin Differentially Modulates Toll-Like Receptor-Stimulated Activation, Migration and T Cell Stimulatory Capacity of Dendritic Cells Adkins, Irena Kamanova, Jana Kocourkova, Aneta Svedova, Martina Tomala, Jakub Janova, Hana Masin, Jiri Chladkova, Barbora Bumba, Ladislav Kovar, Marek Ross, Padraig J. Tuckova, Ludmila Spisek, Radek Mills, Kingston H. G. Sebo, Peter PLoS One Research Article Adenylate cyclase toxin (CyaA) is a key virulence factor of the whooping cough agent Bordetella pertussis. The toxin targets CD11b-expressing phagocytes and delivers into their cytosol an adenylyl cyclase (AC) enzyme that subverts cellular signaling by increasing cAMP levels. In the present study, we analyzed the modulatory effects of CyaA on adhesive, migratory and antigen presenting properties of Toll-like receptor (TLR)-activated murine and human dendritic cells (DCs). cAMP signaling of CyaA enhanced TLR-induced dissolution of cell adhesive contacts and migration of DCs towards the lymph node-homing chemokines CCL19 and CCL21 in vitro. Moreover, we examined in detail the capacity of toxin-treated DCs to induce CD4(+) and CD8(+) T cell responses. Exposure to CyaA decreased the capacity of LPS-stimulated DCs to present soluble protein antigen to CD4(+) T cells independently of modulation of co-stimulatory molecules and cytokine production, and enhanced their capacity to promote CD4(+)CD25(+)Foxp3(+) T regulatory cells in vitro. In addition, CyaA decreased the capacity of LPS-stimulated DCs to induce CD8(+) T cell proliferation and limited the induction of IFN-γ producing CD8(+) T cells while enhancing IL-10 and IL-17-production. These results indicate that through activation of cAMP signaling, the CyaA may be mobilizing DCs impaired in T cell stimulatory capacity and arrival of such DCs into draining lymph nodes may than contribute to delay and subversion of host immune responses during B. pertussis infection. Public Library of Science 2014-08-01 /pmc/articles/PMC4118975/ /pubmed/25084094 http://dx.doi.org/10.1371/journal.pone.0104064 Text en © 2014 Adkins et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Adkins, Irena
Kamanova, Jana
Kocourkova, Aneta
Svedova, Martina
Tomala, Jakub
Janova, Hana
Masin, Jiri
Chladkova, Barbora
Bumba, Ladislav
Kovar, Marek
Ross, Padraig J.
Tuckova, Ludmila
Spisek, Radek
Mills, Kingston H. G.
Sebo, Peter
Bordetella Adenylate Cyclase Toxin Differentially Modulates Toll-Like Receptor-Stimulated Activation, Migration and T Cell Stimulatory Capacity of Dendritic Cells
title Bordetella Adenylate Cyclase Toxin Differentially Modulates Toll-Like Receptor-Stimulated Activation, Migration and T Cell Stimulatory Capacity of Dendritic Cells
title_full Bordetella Adenylate Cyclase Toxin Differentially Modulates Toll-Like Receptor-Stimulated Activation, Migration and T Cell Stimulatory Capacity of Dendritic Cells
title_fullStr Bordetella Adenylate Cyclase Toxin Differentially Modulates Toll-Like Receptor-Stimulated Activation, Migration and T Cell Stimulatory Capacity of Dendritic Cells
title_full_unstemmed Bordetella Adenylate Cyclase Toxin Differentially Modulates Toll-Like Receptor-Stimulated Activation, Migration and T Cell Stimulatory Capacity of Dendritic Cells
title_short Bordetella Adenylate Cyclase Toxin Differentially Modulates Toll-Like Receptor-Stimulated Activation, Migration and T Cell Stimulatory Capacity of Dendritic Cells
title_sort bordetella adenylate cyclase toxin differentially modulates toll-like receptor-stimulated activation, migration and t cell stimulatory capacity of dendritic cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4118975/
https://www.ncbi.nlm.nih.gov/pubmed/25084094
http://dx.doi.org/10.1371/journal.pone.0104064
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