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This article is the author’s final published version in Cell Reports, Volume 29, Issue 10, December 2019, Pages 3047-3059.e3.

The published version is available at Copyright © Wong et al.

Publication made possible in part by support from the Thomas Jefferson University + Philadelphia University Open Access Fund


During disseminating viral infections, a swift innate immune response (IIR) in the draining lymph node (dLN) that restricts systemic viral spread is critical for optimal resistance to disease. However, it is unclear how this IIR is orchestrated. We show that after footpad infection of mice with ectromelia virus, dendritic cells (DCs) highly expressing major histocompatibility complex class II (MHC class IIhi DCs), including CD207+ epidermal Langerhans cells (LCs), CD103+CD207+ double-positive dermal DCs (DP-DCs), and CD103CD207 double-negative dermal DCs (DN-DCs) migrate to the dLN from the skin carrying virus. MHC class IIhi DCs, predominantly LCs and DP-DCs, are the first cells upregulating IIR cytokines in the dLN. Preventing MHC class IIhi DC migration or depletion of LCs, but not DP-DC deficiency, suppresses the IIR in the dLN and results in high viral lethality. Therefore, LCs are the architects of an early IIR in the dLN that is critical for optimal resistance to a disseminating viral infection. Wong et al. show that by producing chemokines that recruit monocytes and by upregulating NKG2D ligands that activate ILCs, Langerhans cells are responsible for the innate immune cascade in the lymph node that is critical for survival of infection with a disseminating virus.

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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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