title: Susceptibility to vaccinia virus infection and spread in mice is determined by age at infection, allergen sensitization and mast cell status.
abstract: BACKGROUND
  Patients, especially young children, with atopic dermatitis are at an increased risk of developing eczema vaccinatum, a severe reaction to the smallpox vaccine, either through direct vaccination or indirect contact with a person recently vaccinated.
  
  
  METHODS
  Using a mouse model of infection, the severity of vaccinia-induced lesions was assessed from their appearance and viral DNA content. The response to vaccinia inoculation was assessed in young and adult mice, allergen-sensitized mice, and in mast cell-deficient mice.
  
  
  RESULTS
  Young age, sensitization to an allergen prior to infection, and a mast cell deficit, accomplished by using mast cell-deficient mice, resulted in more severe viral lesions at the site of inoculation, according to lesion appearance and viral DNA content. All three factors combined demonstrated maximal susceptibility, characterized by the severity of primary lesions and the development of secondary (satellite) lesions, as occurs in eczema vaccinatum in humans. Resistance to the appearance of satellite lesions could be restored by adoptive transfer of bone marrow-derived mast cells from either wild-type or cathelicidin-related antimicrobial peptide-deficient mice. Primary lesions were more severe following the latter transfer, indicating that cathelicidin-related antimicrobial peptide does contribute to the protective activity of mast cells against infection.
  
  
  CONCLUSIONS
  The combination of young age, allergen sensitization and a mast cell deficit resulted in the most severe lesions, including satellite lesions. Understanding the factors determining the relative resistance/sensitivity to vaccinia virus will aid in the development of strategies for preventing and treating adverse reactions which can occur after smallpox vaccination.
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA.
authors.forename: Joanne
authors.initials: J
authors.lastname: Domenico
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Lucas
authors.forename: Mayumi
authors.initials: M
authors.lastname: Fujita
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D019264:Adoptive Transfer; D000367:Age Factors; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001854:Bone Marrow Cells / Q000276:immunology; D054804:Cathelicidins / Q000172:deficiency / Q000502:physiology; D003876:Dermatitis, Atopic / Q000276:immunology*; D007114:Immunization; D007617:Kaposi Varicelliform Eruption / Q000276:immunology; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014615:Vaccinia / Q000276:immunology*; D014616:Vaccinia virus / Q000472:pathogenicity*
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins