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Mycobacterium-Infected Dendritic Cells Disseminate Granulomatous Inflammation

The disappearance and reformation of granulomas during tuberculosis has been described using PET/CT/X-ray in both human clinical settings and animal models, but the mechanisms of granuloma reformation during active disease remains unclear. Granulomas can recruit inflammatory dendritic cells (iDCs) t...

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Autores principales: Harding, Jeffrey S., Rayasam, Aditya, Schreiber, Heidi A., Fabry, Zsuzsanna, Sandor, Matyas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626772/
https://www.ncbi.nlm.nih.gov/pubmed/26515292
http://dx.doi.org/10.1038/srep15248
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author Harding, Jeffrey S.
Rayasam, Aditya
Schreiber, Heidi A.
Fabry, Zsuzsanna
Sandor, Matyas
author_facet Harding, Jeffrey S.
Rayasam, Aditya
Schreiber, Heidi A.
Fabry, Zsuzsanna
Sandor, Matyas
author_sort Harding, Jeffrey S.
collection PubMed
description The disappearance and reformation of granulomas during tuberculosis has been described using PET/CT/X-ray in both human clinical settings and animal models, but the mechanisms of granuloma reformation during active disease remains unclear. Granulomas can recruit inflammatory dendritic cells (iDCs) that can regulate local T-cell responses and can carry bacteria into the lymph nodes, which is crucial for generating systemic T-cell responses against mycobacteria. Here, we report that a subset of mycobacterium-infected iDCs are associated with bacteria-specific T-cells in infected tissue, outside the granuloma, and that this results in the formation of new and/or larger multi-focal lesions. Mycobacterium-infected iDCs express less CCR7 and migrate less efficiently compared to the non-infected iDCs, which may support T-cell capture in granulomatous tissue. Capture may reduce antigen availability in the lymph node, thereby decreasing systemic priming, resulting in a possible regulatory loop between systemic T-cell responses and granuloma reformation. T-cell/infected iDCs clusters outside the granuloma can be detected during the acute and chronic phase of BCG and Mtb infection. Our studies suggest a direct role for inflammatory dendritic cells in the dissemination of granulomatous inflammation.
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spelling pubmed-46267722015-11-03 Mycobacterium-Infected Dendritic Cells Disseminate Granulomatous Inflammation Harding, Jeffrey S. Rayasam, Aditya Schreiber, Heidi A. Fabry, Zsuzsanna Sandor, Matyas Sci Rep Article The disappearance and reformation of granulomas during tuberculosis has been described using PET/CT/X-ray in both human clinical settings and animal models, but the mechanisms of granuloma reformation during active disease remains unclear. Granulomas can recruit inflammatory dendritic cells (iDCs) that can regulate local T-cell responses and can carry bacteria into the lymph nodes, which is crucial for generating systemic T-cell responses against mycobacteria. Here, we report that a subset of mycobacterium-infected iDCs are associated with bacteria-specific T-cells in infected tissue, outside the granuloma, and that this results in the formation of new and/or larger multi-focal lesions. Mycobacterium-infected iDCs express less CCR7 and migrate less efficiently compared to the non-infected iDCs, which may support T-cell capture in granulomatous tissue. Capture may reduce antigen availability in the lymph node, thereby decreasing systemic priming, resulting in a possible regulatory loop between systemic T-cell responses and granuloma reformation. T-cell/infected iDCs clusters outside the granuloma can be detected during the acute and chronic phase of BCG and Mtb infection. Our studies suggest a direct role for inflammatory dendritic cells in the dissemination of granulomatous inflammation. Nature Publishing Group 2015-10-30 /pmc/articles/PMC4626772/ /pubmed/26515292 http://dx.doi.org/10.1038/srep15248 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Harding, Jeffrey S.
Rayasam, Aditya
Schreiber, Heidi A.
Fabry, Zsuzsanna
Sandor, Matyas
Mycobacterium-Infected Dendritic Cells Disseminate Granulomatous Inflammation
title Mycobacterium-Infected Dendritic Cells Disseminate Granulomatous Inflammation
title_full Mycobacterium-Infected Dendritic Cells Disseminate Granulomatous Inflammation
title_fullStr Mycobacterium-Infected Dendritic Cells Disseminate Granulomatous Inflammation
title_full_unstemmed Mycobacterium-Infected Dendritic Cells Disseminate Granulomatous Inflammation
title_short Mycobacterium-Infected Dendritic Cells Disseminate Granulomatous Inflammation
title_sort mycobacterium-infected dendritic cells disseminate granulomatous inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626772/
https://www.ncbi.nlm.nih.gov/pubmed/26515292
http://dx.doi.org/10.1038/srep15248
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