Skin immunisation activates an innate lymphoid cell-monocyte axis regulating CD8
| Autor: | Marija, Zaric, Pablo D, Becker, Catherine, Hervouet, Petya, Kalcheva, Andor, Doszpoly, Negin, Blattman, Lauren, A O' Neill, Barbara Ibarzo, Yus, Clement, Cocita, Sung-Yun, Kwon, Andrew H, Baker, Graham M, Lord, Linda S, Klavinskis |
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| Rok vydání: | 2018 |
| Předmět: |
Receptors
CXCR3 Adaptive immunity CD8-Positive T-Lymphocytes Administration Cutaneous Chemokine CXCL9 gag Gene Products Human Immunodeficiency Virus Monocytes Article Mice Animals Humans Skin Vaccines Synthetic Mucous Membrane Adenoviruses Human Vaccination Viral Vaccines Genitalia Female Immunity Innate Cellular immunity Mice Inbred C57BL Disease Models Animal HEK293 Cells Treatment Outcome Virus Diseases Viral infection Host-Pathogen Interactions Female Immunization |
| Zdroj: | Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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