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

TY - JOUR

T1 - Skin immunisation activates an innate lymphoid cell-monocyte axis regulating CD8+ effector recruitment to mucosal tissues

AU - Zaric, Marija

AU - Becker, Pablo D

AU - Hervouet, Catherine

AU - Kalcheva, Petya

AU - Doszpoly, Andor

AU - Blattman, Negin

AU - O'Neill, Lauren A

AU - Ibarzo Yus, Barbara

AU - Cocita, Clement

AU - Kwon, Sung-Yun

AU - Baker, Andrew H.

AU - Lord, Graham M

AU - Klavinskis, Linda

PY - 2019/5/17

Y1 - 2019/5/17

N2 - 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.

AB - 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.

KW - ILC1,CD8+ T cell, effector T cell, mucosal, recruitment

UR - http://www.scopus.com/inward/record.url?scp=85065877862&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-09969-2

DO - 10.1038/s41467-019-09969-2

M3 - Article

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2214

ER -