Migratory Dendritic Cells, Group 1 Innate Lymphoid Cells, and Inflammatory Monocytes Collaborate to Recruit NK Cells to the Virus-Infected Lymph Node

Publication date: 3 July 2018
Source:Cell Reports, Volume 24, Issue 1
Author(s): Eric Wong, Ren-Huan Xu, Daniel Rubio, Avital Lev, Colby Stotesbury, Min Fang, Luis J. Sigal
Circulating natural killer (NK) cells help protect the host from lympho-hematogenous acute viral diseases by rapidly entering draining lymph nodes (dLNs) to curb virus dissemination. Here, we identify a highly choreographed mechanism underlying this process. Using footpad infection with ectromelia virus, a pathogenic DNA virus of mice, we show that TLR9/MyD88 sensing induces NKG2D ligands in virus-infected, skin-derived migratory dendritic cells (mDCs) to induce production of IFN-γ by classical NK cells and other types of group 1 innate lymphoid cells (ILCs) already in dLNs, via NKG2D. Uninfected inflammatory monocytes, also recruited to dLNs by mDCs in a TLR9/MyD88-dependent manner, respond to IFN-γ by secreting CXCL9 for optimal CXCR3-dependent recruitment of circulating NK cells. This work unveils a TLR9/MyD88-dependent mechanism whereby in dLNs, three cell types—mDCs, group 1 ILCs (mostly NK cells), and inflammatory monocytes—coordinate the recruitment of protective circulating NK cells to dLNs.

Graphical abstract

Teaser

Wong et al. show that infected migratory dendritic cells (mDCs) in draining lymph nodes (dLNs) upregulate NKG2D ligands through TLR9/MyD88. This results in NKG2D-dependent IFN-γ production by group 1 innate lymphoid cells, mostly NK cells. IFN-γ induces CXCL9 in uninfected inflammatory monocytes, leading to the recruitment of protective NK cells to dLNs.


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