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Skin immunisation activates an innate lymphoid cell-monocyte axis regulating CD8(+) effector recruitment to mucosal tissues

CD8(+) T cells provide a critical defence from pathogens at mucosal epithelia including the female reproductive tract (FRT). Mucosal immunisation is considered essential to initiate this response, however this is difficult to reconcile with evidence that antigen delivered to skin can recruit protect...

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Autores principales: Zaric, Marija, Becker, Pablo D., Hervouet, Catherine, Kalcheva, Petya, Doszpoly, Andor, Blattman, Negin, A. O’ Neill, Lauren, Yus, Barbara Ibarzo, Cocita, Clement, Kwon, Sung-Yun, Baker, Andrew H., Lord, Graham M., Klavinskis, Linda S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525176/
https://www.ncbi.nlm.nih.gov/pubmed/31101810
http://dx.doi.org/10.1038/s41467-019-09969-2
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author Zaric, Marija
Becker, Pablo D.
Hervouet, Catherine
Kalcheva, Petya
Doszpoly, Andor
Blattman, Negin
A. O’ Neill, Lauren
Yus, Barbara Ibarzo
Cocita, Clement
Kwon, Sung-Yun
Baker, Andrew H.
Lord, Graham M.
Klavinskis, Linda S.
author_facet Zaric, Marija
Becker, Pablo D.
Hervouet, Catherine
Kalcheva, Petya
Doszpoly, Andor
Blattman, Negin
A. O’ Neill, Lauren
Yus, Barbara Ibarzo
Cocita, Clement
Kwon, Sung-Yun
Baker, Andrew H.
Lord, Graham M.
Klavinskis, Linda S.
author_sort Zaric, Marija
collection PubMed
description CD8(+) T cells provide a critical defence from pathogens at mucosal epithelia including the female reproductive tract (FRT). Mucosal immunisation is considered essential to initiate this response, however this is difficult to reconcile with evidence that antigen delivered to skin can recruit protective CD8(+) T cells to mucosal tissues. Here we dissect the underlying mechanism. We show that adenovirus serotype 5 (Ad5) bio-distributes at very low level to non-lymphoid tissues after skin immunisation. This drives the expansion and activation of CD3(−) NK1.1(+) group 1 innate lymphoid cells (ILC1) within the FRT, essential for recruitment of CD8(+) T-cell effectors. Interferon gamma produced by activated ILC1 is critical to licence CD11b(+)Ly6C(+) monocyte production of CXCL9, a chemokine required to recruit skin primed CXCR3(+) CD8(+)T-cells to the FRT. Our findings reveal a novel role for ILC1 to recruit effector CD8(+) T-cells to prevent virus spread and establish immune surveillance at barrier tissues.
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spelling pubmed-65251762019-05-20 Skin immunisation activates an innate lymphoid cell-monocyte axis regulating CD8(+) effector recruitment to mucosal tissues Zaric, Marija Becker, Pablo D. Hervouet, Catherine Kalcheva, Petya Doszpoly, Andor Blattman, Negin A. O’ Neill, Lauren Yus, Barbara Ibarzo Cocita, Clement Kwon, Sung-Yun Baker, Andrew H. Lord, Graham M. Klavinskis, Linda S. Nat Commun Article CD8(+) T cells provide a critical defence from pathogens at mucosal epithelia including the female reproductive tract (FRT). Mucosal immunisation is considered essential to initiate this response, however this is difficult to reconcile with evidence that antigen delivered to skin can recruit protective CD8(+) T cells to mucosal tissues. Here we dissect the underlying mechanism. We show that adenovirus serotype 5 (Ad5) bio-distributes at very low level to non-lymphoid tissues after skin immunisation. This drives the expansion and activation of CD3(−) NK1.1(+) group 1 innate lymphoid cells (ILC1) within the FRT, essential for recruitment of CD8(+) T-cell effectors. Interferon gamma produced by activated ILC1 is critical to licence CD11b(+)Ly6C(+) monocyte production of CXCL9, a chemokine required to recruit skin primed CXCR3(+) CD8(+)T-cells to the FRT. Our findings reveal a novel role for ILC1 to recruit effector CD8(+) T-cells to prevent virus spread and establish immune surveillance at barrier tissues. Nature Publishing Group UK 2019-05-17 /pmc/articles/PMC6525176/ /pubmed/31101810 http://dx.doi.org/10.1038/s41467-019-09969-2 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zaric, Marija
Becker, Pablo D.
Hervouet, Catherine
Kalcheva, Petya
Doszpoly, Andor
Blattman, Negin
A. O’ Neill, Lauren
Yus, Barbara Ibarzo
Cocita, Clement
Kwon, Sung-Yun
Baker, Andrew H.
Lord, Graham M.
Klavinskis, Linda S.
Skin immunisation activates an innate lymphoid cell-monocyte axis regulating CD8(+) effector recruitment to mucosal tissues
title Skin immunisation activates an innate lymphoid cell-monocyte axis regulating CD8(+) effector recruitment to mucosal tissues
title_full Skin immunisation activates an innate lymphoid cell-monocyte axis regulating CD8(+) effector recruitment to mucosal tissues
title_fullStr Skin immunisation activates an innate lymphoid cell-monocyte axis regulating CD8(+) effector recruitment to mucosal tissues
title_full_unstemmed Skin immunisation activates an innate lymphoid cell-monocyte axis regulating CD8(+) effector recruitment to mucosal tissues
title_short Skin immunisation activates an innate lymphoid cell-monocyte axis regulating CD8(+) effector recruitment to mucosal tissues
title_sort skin immunisation activates an innate lymphoid cell-monocyte axis regulating cd8(+) effector recruitment to mucosal tissues
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525176/
https://www.ncbi.nlm.nih.gov/pubmed/31101810
http://dx.doi.org/10.1038/s41467-019-09969-2
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