Characterization of Resident Corneal Plasmacytoid Dendritic Cells and Their Pivotal Role in Herpes Simplex Keratitis

The presence and potential functions of resident plasmacytoid dendritic cells (pDCs) in peripheral tissues is unclear. We report that pDCs constitutively populate naïve corneas and are increased during sterile injuries or acute herpes simplex virus 1 (HSV-1) keratitis. Their local depletion leads to severe clinical disease, nerve loss, viral dissemination to the trigeminal ganglion and draining lymph nodes, and mortality, while their local adoptive transfer limits disease. pDCs are the main source of HSV-1-induced IFN-α in the corneal stroma through TLR9, and they prevent re-programming of regulatory T cells (Tregs) to effector ex-Tregs. Clinical signs of infection are observed in pDC-depleted corneas, but not in pDC-sufficient corneas, following low-dose HSV-1 inoculation, suggesting their critical role in corneal antiviral immunity. Our findings demonstrate a vital role for corneal pDCs in the control of local viral infections. [Display omitted] •The cornea, as a peripheral barrier, hosts resident pDCs during steady state•Local pDC depletion enhances HSV-1 keratitis severity, nerve damage, and viral spread•pDCs secrete IFN-α via TLR9 and preserve Tregs in the dLNs in acute HSV-1 keratitis•pDCs may protect the cornea from clinical signs of primary HSV-1 corneal infection Jamali et al. show that the cornea, as an immune-privileged tissue, hosts resident pDCs, which mediate immunity against HSV-1 by secreting IFN-α via TLR9 and preserving Tregs. pDCs minimize the clinical severity of HSV-1 keratitis, infiltration of immune cells, nerve damage, and viral dissemination to TG and dLNs.