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dc:abstract "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." ;
dc:creator "['Cush, Stephanie S.', 'Reynoso, Glennys V.', 'Kamenyeva, Olena', 'Bennink, Jack R.', 'Yewdell, Jonathan W.', 'Hickman, Heather D.']" ;
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dc:issued "2016-01-01"^^xsd:date ;
dc:license "CC0" ;
dc:title "Locally Produced IL-10 Limits Cutaneous Vaccinia Virus Spread" ;
sso:has_full_text "True" ;
sso:journal "PLoS Pathog" ;
sso:sha "bfdf1cc025285b3c20fdde66f5de3be60b46930e" ;
sso:source_x "PMC" .