Studies in mice have demonstrated a TLR9-and MyD88-dependent protective role of local CpG administration following intravaginal infection with HSV-2 [160] . pDCs were recruited in the vaginal mucosa 24 hours after CpG treatment. Anti-BST2 antibody-mediated pDC depletion in vivo abrogated the protection. In humans with genital infection by HSV, topical application on the affected regions of a cream formulation of a TLR7 agonist, imiquimod, allows remission of the lesions [161] , likely through the local recruitment and activation of pDCs for IFN-I production. Importantly, this treatment has proven efficient even in the case of recurrent lesions caused by viruses resistant to the classical antiviral drug acyclovir [161] . This was the case for an AIDS-patient whose pDCs were unable to respond to HSV-1 upon in vitro restimulation but produced high levels of IFN-I upon exposure to imiquimod [54] . Thus, boosting pDC responses on genital lesions caused by herpesviruses, through the local administration of TLR7 or 9 agonists, can lead to efficient control of the virus and cure of the disease through activation of antiviral innate immunity, in complement or alternatively to the use of classical antiviral drugs directly inhibiting the viral DNA polymerase (Scheme 2).