title: Anatomically restricted synergistic antiviral activities of innate and adaptive immune cells in the skin.
abstract: Despite extensive ex vivo investigation, the spatiotemporal organization of immune cells interacting with virus-infected cells in tissues remains uncertain. To address this, we used intravital multiphoton microscopy to visualize immune cell interactions with virus-infected cells following epicutaneous vaccinia virus (VV) infection of mice. VV infects keratinocytes in epidermal foci and numerous migratory dermal inflammatory monocytes that outlie the foci. We observed Ly6G(+) innate immune cells infiltrating and controlling foci, while CD8(+) T cells remained on the periphery killing infected monocytes. Most antigen-specific CD8(+) T cells in the skin did not interact with virus-infected cells. Blocking the generation of reactive nitrogen species relocated CD8(+) T cells into foci, modestly reducing viral titers. Depletion of Ly6G(+) and CD8(+) cells dramatically increased viral titers, consistent with their synergistic but spatially segregated viral clearance activities. These findings highlight previously unappreciated differences in the anatomic specialization of antiviral immune cell subsets.
authors: Laboratory of Viral Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Heather D
authors: HD
authors: Hickman
authors: Glennys V
authors: GV
authors: Reynoso
authors: Barbara F
authors: BF
authors: Ngudiankama
authors: Erica J
authors: EJ
authors: Rubin
authors: Javier G
authors: JG
authors: Magadán
authors: Stephanie S
authors: SS
authors: Cush
authors: James
authors: J
authors: Gibbs
authors: Barbara
authors: B
authors: Molon
authors: Vincenzo
authors: V
authors: Bronte
authors: Jack R
authors: JR
authors: Bennink
authors: Jonathan W
authors: JW
authors: Yewdell
mesh_terms: D056704:Adaptive Immunity; D000279:Administration, Cutaneous; D000818:Animals; D000950:Antigens, Ly / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002465:Cell Movement; D018925:Chemokines / Q000276:immunology; D004817:Epidermis / Q000276:immunology / Q000473:pathology* / Q000821:virology; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D015603:Keratinocytes / Q000821:virology; D051379:Mice; D036641:Microscopy, Fluorescence, Multiphoton; D009000:Monocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D030421:Peroxynitrous Acid / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017193:Skin Diseases, Viral / Q000276:immunology / Q000821:virology; D014615:Vaccinia / Q000276:immunology / Q000821:virology; D014616:Vaccinia virus / Q000276:immunology*; D019562:Viral Load
chemical_list: D000950:Antigens, Ly; D018925:Chemokines; C480309:Ly6G antigen, mouse; D026361:Reactive Nitrogen Species; D030421:Peroxynitrous Acid