Locally Produced IL-10 Limits Cutaneous Vaccinia Virus Spread

Skin infection with the poxvirus vaccinia (vv) elicits a powerful,inflammatory cellular response that clears virus infection in a coordinated,spatially organized manner. given the high concentration of pro-inflammatory effectors at areas of viral infection,it is unclear how tissue pathology is limited while virus-infected cells are being eliminated. to better understand the spatial dynamics of the anti-inflammatory response to a cutaneous viral infection,we first screened cytokine mrna expression levels after epicutaneous (ec.) vv infection and found a large increase the anti-inflammatory cytokine il-10. ex vivo analyses revealed that t cells in the skin were the primary il-10-producing cells. to understand the distribution of il-10-producing t cells in vivo,we performed multiphoton intravital microscopy (mpm) of vv-infected mice,assessing the location and dynamic behavior of il-10 producing cells. although virus-specific t cells were distributed throughout areas of the inflamed skin lacking overt virus-infection,il-10+ cells closely associated with large keratinocytic foci of virus replication where they exhibited similar motility patterns to bulk antigen-specific cd8+ t cells. paradoxically,neutralizing secreted il-10 in vivo with an anti-il-10 antibody increased viral lesion size and viral replication. additional analyses demonstrated that il-10 antibody administration decreased recruitment of ccr2+ inflammatory monocytes,which were important for reducing viral burden in the infected skin. based upon these findings,we conclude that spatially concentrated il-10 production limits cutaneous viral replication and dissemination,likely through modulation of the innate immune repertoire at the site of viral growth. © 2016 public library of science. all rights reserved.