title: Immune escape phenomenon in molluscum contagiosum and the induction of apoptosis.
abstract: Molluscum contagiosum (MC) may persist for many weeks, evading host immunity. We studied the mechanism of immune escape phenomenon in MC, and the possible inducer of apoptosis. Using tissue samples of MC, we examined the numbers of epidermal Langerhans cells (LC), the expression levels of macrophage inflammatory protein-3α (MIP-3α) and thymic stromal lymphopoietin (TSLP), and the apoptotic signals. After molluscum contagiosum virus (MCV) genotyping, we studied the expression of MCV-encoded MC148 mRNA and MC159 mRNA which correspond to viral antagonist for CCR8 and viral Fas-linked interleukin (IL)-1β converting enzyme (FLICE)-like inhibitor protein (vFLIP), respectively. The nutlin-3-induced apoptosis in MC was observed ex vivo. The numbers of CD1a(+) or Langerin(+) epidermal LC and the expression levels of MIP-3α were markedly decreased in MC. The expression of TSLP was enhanced in the lesional epidermis of atopic dermatitis and human papillomavirus-induced warts, whereas the expression was observed locally in MC. All 14 MC samples examined harbored MCV type 1. The MC148 mRNA was detected in all 14 samples and the MC159 mRNA was detected in 13 samples. Apoptotic cells were absent or at a background level in the living layers of MC, but their numbers were increased in the molluscum bodies by overnight incubation with 5 μmol/L nutlin-3 in culture medium. In conclusion, molluscum bodies are protected from host immune responses and apoptotic signals by being surrounded by LC-depleted epidermal walls and viral immunosuppressive molecules, but could be eradicated by reagents inducing p53-dependent apoptosis.
authors.affiliation: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Yamauchi-Yamada
authors.forename: Takenobu
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Yumi
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Kazuko
authors.initials: K
authors.lastname: Ikeda
authors.forename: Tomoko
authors.initials: T
authors.lastname: Miyake
authors.forename: Mari
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Yoji
authors.initials: Y
authors.lastname: Hirai
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Shirafuji
authors.forename: Shin
authors.initials: S
authors.lastname: Morizane
authors.forename: Yumi
authors.initials: Y
authors.lastname: Aoyama
authors.forename: Keiji
authors.initials: K
authors.lastname: Iwatsuki
mesh_terms: D017209:Apoptosis; D054418:Chemokine CCL20 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007093:Imidazoles; D007801:Langerhans Cells; D008976:Molluscum Contagiosum / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010879:Piperazines; D014860:Warts / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: C108355:CCL20 protein, human; D054418:Chemokine CCL20; D016207:Cytokines; D007093:Imidazoles; D010879:Piperazines; C482205:nutlin 3; D000094632:Thymic Stromal Lymphopoietin
keywords: Langerhans cell; dendritic cell; macrophage inflammatory protein-3α; molluscum contagiosum virus; nutlin-3