Pan-viral protection against arboviruses by activating skin macrophages at the inoculation site
Steven R. Bryden, Marieke Pingen, Daniella Lefteri, Janne Miltenburg, Leen Delang, Sofie Jacobs, Rana Abdelnabi, Johan Neyts, Emilie Pondeville, Jack Major, Marietta Müller, Henna Khalid, Andrew Tuplin, Margus Varjak, Andres Merits, Julia M. Edgar, Gerard J. Graham, Kave Shams, Clive S. McKimmie
Abstract
genera. Clinical outcome was improved in mice after infection with a model alphavirus. In the absence of treatment, antiviral interferon expression to virus in the skin was restricted to dermal dendritic cells. In contrast, stimulating the more populous skin-resident macrophages with a TLR7 agonist elicited protective responses in key cellular targets of virus that otherwise proficiently replicated virus. By defining and targeting a key aspect of the innate immune response to virus at the mosquito bite site, we have identified a putative new strategy for limiting disease after infection with a variety of genetically distinct arboviruses.