Complement mediated signaling on pulmonary CD103(+) dendritic cells is critical for their migratory function in response to influenza infection.

Trafficking of lung dendritic cells (DCs) to the draining lymph node (dLN) is a crucial step for the initiation of T cell responses upon pathogen challenge. However, little is known about the factors that regulate lung DC migration to the dLN. In this study, using a model of influenza infection, we...

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Autores principales: Matheswaran Kandasamy, Poon C Ying, Adrian W S Ho, Hermi R Sumatoh, Andreas Schlitzer, Timothy R Hughes, David M Kemeny, B Paul Morgan, Florent Ginhoux, Baalasubramanian Sivasankar
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/8999718c41124fd0a4b58773d930607c
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spelling oai:doaj.org-article:8999718c41124fd0a4b58773d930607c2021-11-18T06:06:10ZComplement mediated signaling on pulmonary CD103(+) dendritic cells is critical for their migratory function in response to influenza infection.1553-73661553-737410.1371/journal.ppat.1003115https://doaj.org/article/8999718c41124fd0a4b58773d930607c2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23326231/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Trafficking of lung dendritic cells (DCs) to the draining lymph node (dLN) is a crucial step for the initiation of T cell responses upon pathogen challenge. However, little is known about the factors that regulate lung DC migration to the dLN. In this study, using a model of influenza infection, we demonstrate that complement component C3 is critically required for efficient emigration of DCs from the lung to the dLN. C3 deficiency affect lung DC-mediated viral antigen transport to the dLN, resulting in severely compromised priming of virus-specific T cell responses. Consequently, C3-deficient mice lack effector T cell response in the lungs that affected viral clearance and survival. We further show that direct signaling by C3a and C5a through C3aR and C5aR respectively expressed on lung DCs is required for their efficient trafficking. However, among lung DCs, only CD103(+) DCs make a significant contribution to lung C5a levels and exclusively produce high levels of C3 and C5 during influenza infection. Collectively, our findings show that complement has a profound impact on immune regulation by controlling tissue DC trafficking and highlights a potential utility for complement as an adjuvant in novel vaccine strategies.Matheswaran KandasamyPoon C YingAdrian W S HoHermi R SumatohAndreas SchlitzerTimothy R HughesDavid M KemenyB Paul MorganFlorent GinhouxBaalasubramanian SivasankarPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 1, p e1003115 (2013)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
spellingShingle Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Matheswaran Kandasamy
Poon C Ying
Adrian W S Ho
Hermi R Sumatoh
Andreas Schlitzer
Timothy R Hughes
David M Kemeny
B Paul Morgan
Florent Ginhoux
Baalasubramanian Sivasankar
Complement mediated signaling on pulmonary CD103(+) dendritic cells is critical for their migratory function in response to influenza infection.
description Trafficking of lung dendritic cells (DCs) to the draining lymph node (dLN) is a crucial step for the initiation of T cell responses upon pathogen challenge. However, little is known about the factors that regulate lung DC migration to the dLN. In this study, using a model of influenza infection, we demonstrate that complement component C3 is critically required for efficient emigration of DCs from the lung to the dLN. C3 deficiency affect lung DC-mediated viral antigen transport to the dLN, resulting in severely compromised priming of virus-specific T cell responses. Consequently, C3-deficient mice lack effector T cell response in the lungs that affected viral clearance and survival. We further show that direct signaling by C3a and C5a through C3aR and C5aR respectively expressed on lung DCs is required for their efficient trafficking. However, among lung DCs, only CD103(+) DCs make a significant contribution to lung C5a levels and exclusively produce high levels of C3 and C5 during influenza infection. Collectively, our findings show that complement has a profound impact on immune regulation by controlling tissue DC trafficking and highlights a potential utility for complement as an adjuvant in novel vaccine strategies.
format article
author Matheswaran Kandasamy
Poon C Ying
Adrian W S Ho
Hermi R Sumatoh
Andreas Schlitzer
Timothy R Hughes
David M Kemeny
B Paul Morgan
Florent Ginhoux
Baalasubramanian Sivasankar
author_facet Matheswaran Kandasamy
Poon C Ying
Adrian W S Ho
Hermi R Sumatoh
Andreas Schlitzer
Timothy R Hughes
David M Kemeny
B Paul Morgan
Florent Ginhoux
Baalasubramanian Sivasankar
author_sort Matheswaran Kandasamy
title Complement mediated signaling on pulmonary CD103(+) dendritic cells is critical for their migratory function in response to influenza infection.
title_short Complement mediated signaling on pulmonary CD103(+) dendritic cells is critical for their migratory function in response to influenza infection.
title_full Complement mediated signaling on pulmonary CD103(+) dendritic cells is critical for their migratory function in response to influenza infection.
title_fullStr Complement mediated signaling on pulmonary CD103(+) dendritic cells is critical for their migratory function in response to influenza infection.
title_full_unstemmed Complement mediated signaling on pulmonary CD103(+) dendritic cells is critical for their migratory function in response to influenza infection.
title_sort complement mediated signaling on pulmonary cd103(+) dendritic cells is critical for their migratory function in response to influenza infection.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/8999718c41124fd0a4b58773d930607c
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