Filaggrin deficiency promotes the dissemination of cutaneously inoculated vaccinia virus.

Journal Article (Journal Article)


Eczema vaccinatum is a life-threatening complication of smallpox vaccination in patients with atopic dermatitis (AD) characterized by dissemination of vaccinia virus (VV) in the skin and internal organs. Mutations in the filaggrin (FLG) gene, the most common genetic risk factor for AD, confer a greater risk for eczema herpeticum in patients with AD, suggesting that it impairs the response to cutaneous viral infections.


We sought to determine the effects of FLG deficiency on the response of mice to cutaneous VV inoculation.


VV was inoculated by means of scarification of unsensitized skin or skin topically sensitized with ovalbumin in FLG-deficient flaky tail (ft/ft) mice or wild-type (WT) control mice. The sizes of primary and satellite skin lesions were measured, and hematoxylin and eosin staining was performed. VV genome copy numbers and cytokine mRNA levels were measured by using quantitative PCR.


VV inoculation in unsensitized skin of ft/ft mice, independent of the matted hair mutation, resulted in larger primary lesions, more abundant satellite lesions, heavier viral loads in internal organs, greater epidermal thickness, dermal cellular infiltration, and higher local Il17a, Il4, Il13, and Ifng mRNA levels than in WT control mice. VV inoculation at sites of topical ovalbumin application amplified all of these features in ft/ft mice but had no detectable effect in WT control mice. The number of satellite lesions and the viral loads in internal organs after cutaneous VV inoculation were significantly reduced in both unsensitized and topically sensitized ft/ftxIl17a(-/-) mice.


FLG deficiency predisposes to eczema vaccinatum. This is mediated primarily through production of IL-17A.

Full Text

Duke Authors

Cited Authors

  • Oyoshi, MK; Beaupré, J; Venturelli, N; Lewis, CN; Iwakura, Y; Geha, RS

Published Date

  • June 2015

Published In

Volume / Issue

  • 135 / 6

Start / End Page

  • 1511 - 8.e6

PubMed ID

  • 25649082

Pubmed Central ID

  • PMC4461532

Electronic International Standard Serial Number (EISSN)

  • 1097-6825

International Standard Serial Number (ISSN)

  • 0091-6749

Digital Object Identifier (DOI)

  • 10.1016/j.jaci.2014.12.1923


  • eng