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 CD103−CD207− 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.
Wong, Eric B.; Montoya, Brian; Stotesbury, Colby; Ferez, Maria; Xu, Ren-Huan; and Sigal, Luis J., "Langerhans Cells Orchestrate the Protective Antiviral Innate Immune Response in the Lymph Node." (2019). Department of Microbiology and Immunology Faculty Papers. Paper 112.
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