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 protecti...

Full description

Saved in:

Bibliographic Details
Published in:	Nature communications Vol. 10; no. 1; p. 2214
Main Authors:	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.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 17-05-2019 Nature Publishing Group Nature Portfolio
Subjects:	13/1 13/106 13/31 13/44 631/250/2152 631/250/2152/1566 631/250/251/1567 631/250/255/2514 Adenoviruses, Human - genetics Adenoviruses, Human - immunology Administration, Cutaneous Animals Antigens CD11b antigen CD3 antigen CD8 antigen CD8-Positive T-Lymphocytes - immunology Chemokine CXCL9 Chemokines CXCR3 protein Disease Models, Animal Effector cells Female gag Gene Products, Human Immunodeficiency Virus - genetics gag Gene Products, Human Immunodeficiency Virus - immunology Genitalia, Female - cytology Genitalia, Female - immunology Genitalia, Female - virology HEK293 Cells Host-Pathogen Interactions - immunology Humanities and Social Sciences Humans Immunity, Innate Immunization Immunosurveillance Interferon Low level Lymphocytes Lymphocytes T Lymphoid cells Lymphoid tissue Mice Mice, Inbred C57BL Monocytes Monocytes - immunology Mucosa Mucous Membrane - cytology Mucous Membrane - immunology Mucous Membrane - virology multidisciplinary Receptors, CXCR3 Recruitment Reproductive system Science Science (multidisciplinary) Skin Skin - cytology Skin - immunology Skin - virology Tissues Treatment Outcome Vaccination - methods Vaccines, Synthetic - administration & dosage Vaccines, Synthetic - genetics Vaccines, Synthetic - immunology Viral Vaccines - administration & dosage Viral Vaccines - genetics Viral Vaccines - immunology Virus Diseases - immunology Virus Diseases - prevention & control Virus Diseases - virology Viruses
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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. Mucosal immunisation is important for initiating mucosal CD8 + Tcell responses but mucosal recruitment of protective CD8 + T cells can also be induced by skin immunisation. Here the authors examine the underlying mechanism and report a novel role for ILC1 recruiting CD8 + T cells to the mucosa after skin immunisation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-019-09969-2