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Wong E , Xu RH , Rubio D , Lev A , Stotesbury C , Fang M , Sigal LJ
Migratory Dendritic Cells, Group 1 Innate Lymphoid Cells, and Inflammatory Monocytes Collaborate to Recruit NK Cells to the Virus-Infected Lymph Node
Cell Reports. 2018 Jul 3;24(1) :142-154
PMID: 29972776    PMCID: PMC6232077    URL: https://www.ncbi.nlm.nih.gov/pubmed/29972776
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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-gamma 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-gamma 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.
Export Date: 2 July 2018 Article in Press F32 AI129352/AI/NIAID NIH HHS/ R01 AG048602/AG/NIA NIH HHS/ R01 AI065544/AI/NIAID NIH HHS/ R01 AI110457/AI/NIAID NIH HHS/