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Defensins induce the recruitment of dendritic cells in cervical human papillomavirus‐associated (pre)neoplastic lesions formed in vitro and transplanted in vivo
Author(s) -
Hubert Pascale,
Herman Ludivine,
Maillard Catherine,
Caberg JeanHubert,
Nikkels Arjen,
Pierard Gerald,
Foidart JeanMarie,
Noel Agnes,
Boniver Jacques,
Delvenne Philippe
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-7646com
Subject(s) - in vivo , biology , beta defensin , in vitro , immune system , defensin , pathology , epithelium , transplantation , cancer research , immunology , innate immune system , medicine , microbiology and biotechnology , antimicrobial , biochemistry
In addition to their direct antimicrobial activity, defensins might also influence adaptive immu‐nity by attracting immature dendritic cells (DC). As these cells have been shown to be deficient in uterine cervix carcinogenesis, we evaluated the ability of a‐de‐fensin (HNP‐2, human neutrophil defensin 2) and ß‐defensin (HßD2, human beta defensin 2) to stimulate their migration in human papillomavirus (HPV)‐associated (pre)cancers. We first observed, using RT‐PCR and immunohistology, that HßD2 is absent in HPV‐transformed keratinocytes and that it is weakly expressed in cervical (pre)neoplastic lesions in comparison with normal keratinocytes. We next demonstrated that defensins exert a chemotactic activity for DC in a Boyden Chamber assay and stimulate their infiltration in an in vitro ‐formed (pre)neoplastic epithelium (orga‐notypic culture of HPV‐transformed keratinocytes). To evaluate the ability of defensins also to recruit DC in vivo, we developed a model of immunodeficient mice grafted with organotypic cultures of HPV + keratino‐cytes, which form an epithelium similar to a high‐grade neoplastic lesion, with tumoral invasion and neovascu‐larization. Intravenously injected human DC were able to infiltrate grafts of HPV + keratinocytes after administration of HNP‐2 in the transplantation chamber. Taken together, these results suggest that defensins could reverse a frequent immune alteration observed in cancer development.—Hubert, P., Herman, L., Maillard, C., Caberg, J‐H., Nikkels, A., Pierard, G., Foidart, J‐M., Noel, A., Boniver, J., Delvenne, P. Defensins induce the recruitment of dendritic cells in cervical human papillomavirus‐associated (pre)neoplastic lesions formed in vitro and transplanted in vivo. FASEB J. 21, 2765–2775 (2007)