Spontaneous regression of highly immunogenic molluscum contagiosum virus (MCV)-induced skin lesions is associated with plasmacytoid dendritic cells and IFN-DC infiltration

William Vermi, Simona Fisogni, Laura Salogni, Leo Schärer, Heinz Kutzner, Silvano Sozzani, Silvia Lonardi, Cristina Rossini, Piergiacomo Calzavara-Pinton, Philip E. Leboit, Fabio Facchetti

Research output: Contribution to journalArticlepeer-review

Abstract

Molluscum contagiosum virus (MCV) infection induces self-limiting cutaneous lesions in an immunocompetent host that can undergo spontaneous regression preceded by local inflammation. On histology, a large majority of MCV-induced lesions are characterized by islands of hyperplastic epithelium containing infected keratinocytes and surrounded by scarce inflammatory infiltrate. However, spontaneous regression has been associated with the occurrence of a dense inflammatory reaction. By histology and immunohistochemistry, we identified MCV-induced lesions showing a dense inflammatory infiltrate associated with cell death in keratinocytes (inflammatory Molluscum contagiosum (I-MC)). In I-MC, hyperplastic keratinocytes were highly immunogenic as demonstrated by the expression of major histocompatibility complex class I and II molecules. Immune cell infiltration consisted of numerous cytotoxic T cells admixed with natural killer cells and plasmacytoid dendritic cells (PDCs). Accordingly, a type I IFN signature associated with PDC infiltration was demonstrated in both keratinocytes and inflammatory cells. Among the latter, a cell population resembling IFN-DC (CD123+ CD11c+ CD16 + CD14+ MxA+ ) was identified in proximity to islands of apoptotic keratinocytes. In vitro-generated IFN-DCs expressed a strong cytotoxic signature, as demonstrated by high levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL). This study establishes a previously unreported model to underpin the role of innate immune cells in viral immune surveillance.

Original languageEnglish
Pages (from-to)426-434
Number of pages9
JournalJournal of Investigative Dermatology
Volume131
Issue number2
DOIs
Publication statusPublished - Feb 2011

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

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