Spontaneous regression of highly immunogenic Molluscum contagiosum virus (MCV)-induced skin lesions is associated with plasmacytoid dendritic cells and IFN-DC infiltration.
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.
Vermi
William
W
Department of Pathology, University of Brescia, Brescia, Italy.
Fisogni
Simona
S
Salogni
Laura
L
Schärer
Leo
L
Kutzner
Heinz
H
Sozzani
Silvano
S
Lonardi
Silvia
S
Rossini
Cristina
C
Calzavara-Pinton
Piergiacomo
P
LeBoit
Philip E
PE
Facchetti
Fabio
F
D000818:Animals; D017209:Apoptosis; D001706:Biopsy; D039521:CD11c Antigen; D002450:Cell Communication; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology*; D053222:Fas Ligand Protein / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007370:Interferon Type I / Q000378:metabolism*; D053650:Interleukin-3 Receptor alpha Subunit; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008976:Molluscum Contagiosum / Q000473:pathology* / Q000821:virology*; D008977:Molluscum contagiosum virus / Q000302:isolation & purification*; D012867:Skin / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism
D039521:CD11c Antigen; D053222:Fas Ligand Protein; D007370:Interferon Type I; D053650:Interleukin-3 Receptor alpha Subunit; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human