Defensis induce the recruitment of dendritic cells in cervical human papillomavirus-associated (pre)neoplastic lesions formed in vitro and transplanted in vivo
[en] In addition to their direct antimicrobial activity, defensins might also influence adaptive immunity by attracting immature dendritic cells (DC). As these cells have been shown to be deficient in uterine cervix carcinogenesis, we evaluated the ability of -defensin (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 (organotypic 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+ keratinocytes, which form an epithelium similar to a high-grade neoplastic lesion, with tumoral invasion and neovascularization. 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.
Nikkels, Arjen ; Université de Liège - ULiège > Département des sciences cliniques > Dermatologie
Pierard, Gérald ; Université de Liège - ULiège > Département des sciences cliniques > Dermatopathologie
Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique - Labo de biologie des tumeurs et du développement
Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Boniver, Jacques ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Delvenne, Philippe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Language :
English
Title :
Defensis induce the recruitment of dendritic cells in cervical human papillomavirus-associated (pre)neoplastic lesions formed in vitro and transplanted in vivo
Publication date :
2007
Journal title :
FASEB Journal
ISSN :
0892-6638
eISSN :
1530-6860
Publisher :
Federation of American Society for Experimental Biology, Bethesda, United States - Maryland
Bosch, F. X., and Munoz, N. (2002) The viral etiology of cervical cancer. Virus Res. 89, 183-190
Al-Saleh, W., Giannini, S. L., Jacobs, N., Moutchen, M., Doyen, J., Boniver, J., and Delvenne, P. (1998) Correlation of T-helper secretory differentiation and types of antigen-presenting cells in squamous intraepithelial lesions of the uterine cervix. J. Pathol. 184, 283-290
Calore, E. E., Cavaliere, M. J., Perez Calore, N. M., de Souza Dias, S., Paes Dos Santos, R., and Vilela-De-Almeida, L. (2001) Expression of Ki-67 in cervical epithelial cells in preneoplastic lesions of patients with AIDS. Gynecol. Obstet. Invest. 51, 51-54
Thivolet, J., Viac, J., and Staquet, M. J. (1982) Cell-mediated immunity in wart infection. Int. J. Dermatol. 21, 94-98
Hughes, R. G., Norval, M., and Howie, S. E. (1988) Expression of major histocompatibility class II antigens by Langerhans' cells in cervical intraepithelial neoplasia. J. Clin. Pathol. 41, 253-259
Memar, O. M., Arany, I., and Tyring, S. K. (1995) Skin-associated lymphoid tissue in human immunodeficiency virus-1, human papillomavirus, and herpes simplex virus infections. J. Invest Dermatol. 105, 99S-104S
Giannini, S. L., Hubert, P., Doyen, J., Boniver, J., and Delvenne, P. (2002) Influence of the mucosal epithelium microenvironment on Langerhans cells: implications for the development of squamous intraepithelial lesions of the cervix. Int. J. Cancer. 97, 654-659
Hubert, P., Greimers, R., Franzen-Detrooz, E., Doyen, J., Delanoye, P., Boniver, J., and Delvenne, P. (1998) In vitro propagated dendritic cells from patients with human-papilloma virus-associated preneoplastic lesions of the uterine cervix: use of Flt3 ligand. Cancer Immunol. Immunother. 47, 81-89
Charbonnier, A. S., Kohrgruber, N., Kriehuber, E., Stingl, G., Rot, A., and Maurer, D. (1999) Macrophage inflammatory protein 3alpha is involved in the constitutive trafficking of epidermal langerhans cells. J. Exp. Med. 190, 1755-1768
Yang, D., Chertov, O., Bykovskaia, S. N., Chen, Q., Buffo, M. J., Shogan, J., Anderson, M., Schroder, J. M., Wang, J. M., Howard, O. M., et al. (1999) Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 286, 525-528
Mallow, E. B., Harris, A., Salzman, N., Russell, J. P., DeBerardinis, R. J., Ruchelli, E., and Bevins, C. L. (1996) Human enteric defensins. Gene structure and developmental expression. J. Biol. Chem. 271, 4038-4045
Agerberth, B., Charo, J., Werr, J., Olsson, B., Idali, F., Lindbom, L., Kiessling, R., Jornvall, H., Wigzell, H., and Gudmundsson, G. H. (2000) The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood. 96, 3086-3093
Chen, H., Xu, Z., Peng, L., Fang, X., Yin, X., Xu, N., and Cen, P. (2006) Recent advances in the research and development of human defensins. Peptides. 27, 931-940
Sorensen, O. E., Thapa, D. R., Rosenthal, A., Liu, L., Roberts, A. A., and Ganz, T. (2005) Differential regulation of beta-defensin expression in human skin by microbial stimuli. J. Immunol. 174, 4870-4879
Yang, D., Chen, Q., Chertov, O., and Oppenheim, J. J. (2000) Human neutrophil defensins selectively chemoattract naive T and immature dendritic cells. J. Leukoc. Biol. 68, 9-14
Delvenne, P., Al-Saleh, W., Gilles, C., Thiry, A., and Boniver, J. (1995) Inhibition of growth of normal and human papillomavirus-transformed keratinocytes in monolayer and organotypic cultures by interferon-G and tumor necrosis factor-A. Am. J. Pathol. 146, 589-598
Josien, R., Heslan, M., Soulillou, J. P., and Cuturi, M. C. (1997) Rat spleen dendritic cells express natural killer cell receptor protein 1 (NKR-P1) and have cytotoxic activity to select targets via a Ca2+-dependent mechanism. J. Exp. Med. 186, 467-472
Bajou, K., Noel, A., Gerard, R. D., Masson, V., Brunner, N., Holst-Hansen, C., Skobe, M., Fusenig, N. E., Carmeliet, P., Collen, D., et al. (1998) Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization. Nat. Med. 4, 923-928
Hubert, P., Van Den Brule, F., Giannini, S. L., Franzen-Detrooz, E., Boniver, J., and Delvenne, P. (1999) Colonization of in vitro-formed cervical human papillomavirus-associated (pre) neoplastic lesions with dendritic cells. Role of granulocyte/macrophage colony-stimulating factor. Am. J. Pathol. 154, 775-784
Pater, M. M., and Pater, A. (1985) Human papillomavirus types 16 and 18 sequences in carcinoma cell lines of the cervix. Virology. 145, 313-318
Friedl, F., Kimura, I., Osato, T., and Ito, Y. (1970) Studies on a new human cell line (SiHa) derived from carcinoma of uterus. I. Its establishment and morphology. Proc. Soc. Exp. Biol. 135, 543-545
Renard, I., Mezzanzanica, D., Canevari, S., Ferrini, S., Boniver, J., Delvenne, P., and Jacobs, N. (2002) Anti-CD3/anti-epidermal growth factor receptor-bispecific antibody retargeting of lymphocytes against human neoplastic keratinocytes in an autologous organotypic culture model. Am. J. Pathol. 160, 113-122
Hubert, P., Caberg, J. H., Gilles, C., Bousarghin, L., Franzen-Detrooz, E., Boniver, J., and Delvenne, P. (2005) E-cadherin-dependent adhesion of dendritic and Langerhans cells to keratinocytes is defective in cervical human papillomavirus-associated (pre)neoplastic lesions. J. Pathol. 206, 346-355
Hubert, P., Giannini, S. L., Vanderplasschen, A., Franzen-Detrooz, E., Jacobs, N., Boniver, J., and Delvenne, P. (2001) Dendritic cells induce the death of human papillomavirus-transformed keratinocytes1. FASEB J. 15, 2521-2523
Hubert, P., Bousarghin, L., Greimers, R., Franzen-Detrooz, E., Boniver, J., and Delvenne, P. (2005) Production of large numbers of Langerhans' cells with intraepithelial migration ability in vitro. Exp. Dermatol. 14, 469-477
Chadebech, P., Goidin, D., Jacquet, C., Viac, J., Schmitt, D., and Staquet, M. J. (2003) Use of human reconstructed epidermis to analyze the regulation of beta-defensin hBD-1, hBD-2, and hBD-3 expression in response to LPS. Cell Biol. Toxicol. 19, 313-324
Duits, L. A., Ravensbergen, B., Rademaker, M., Hiemstra, P. S., and Nibbering, P. H. (2002) Expression of beta-defensin 1 and 2 mRNA by human monocytes, macrophages and dendritic cells. Immunology. 106, 517-525
Andrade, W., Seabrook, T. J., Johnston, M. G., and Hay, J. B. (1996) The use of the lipophilic fluorochrome CM-DiI for tracking the migration of lymphocytes. J. Immunol. Methods 194, 181-189
Chertov, O., Michiel, D. F., Xu, L., Wang, J. M., Tani, K., Murphy, W. J., Longo, D. L., Taub, D. D., and Oppenheim, J. J. (1996) Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils. J. Biol. Chem. 271, 2935-2940
Noel, A., Maillard, C., Rocks, N., Jost, M., Chabottaux, V., Sounni, N. E., Maquoi, E., Cataldo, D., and Foidart, J. M. (2004) Membrane-associated proteases and their inhibitors in tumour angiogenesis. J. Clin. Pathol. 57, 577-584
Weinberg, A., Quinones-Mateu, M. E., and Lederman, M. M. (2006) Role of human beta-defensins in HIV infection. Adv. Dent. Res. 19, 42-48
Wang, W., Owen, S. M., Rudolph, D. L., Cole, A. M., Hong, T., Waring, A. J., Lal, R. B., and Lehrer, R. I. (2004) Activity of alpha- and theta-defensins against primary isolates of HIV-1. J. Immunol. 173, 515-520
Buck, C. B., Day, P. M., Thompson, C. D., Lubkowski, J., Lu, W., Lowy, D. R., and Schiller, J. T. (2006) Human alpha-defensins block papillomavirus infection. Proc. Natl. Acad. Sci. U. S. A. 103, 1516-1521
Papo, N., and Shai, Y. (2005) Host defense peptides as new weapons in cancer treatment. Cell Mol. Life. Sci. 62, 784-790
McKeown, S. T., Lundy, F. T., Nelson, J., Lockhart, D., Irwin, C. R., Cowan, C. G., and Marley, J. J. (2006) The cytotoxic effects of human neutrophil peptide-1 (HNP1) and lactoferrin on oral squamous cell carcinoma (OSCC) in vitro. Oral Oncol 42, 685-690
Kaplan, G., Walsh, G., Guido, L. S., Meyn, P., Burkhardt, R. A., Abalos, R. M., Barker, J., Frindt, P. A., Fajardo, T. T., and Celona, R. (1992) Novel responses of human skin to intradermal recombinant granulocyte/macrophage- colony-stimulating factor: Langerhans cell recruitment, keratinocyte growth, and enhanced wound healing. J. Exp. Med. 175, 1717-1728
Havard, L., Rahmouni, S., Boniver, J., and Delvenne, P. (2005) High levels of p105 (NFKB1) and p100 (NFKB2) proteins in HPV16-transformed keratinocytes: role of E6 and E7 oncoproteins. Virology 331, 357-366
Ali, R. S., Falconer, A., Ikram, M., Bissett, C. E., Cerio, R., and Quinn, A. G. (2001) Expression of the peptide antibiotics human beta defensin-1 and human beta defensin-2 in normal human skin. J. Invest. Dermatol. 117, 106-111
Howell, M. D., Novak, N., Bieber, T., Pastore, S., Girolomoni, G., Boguniewicz, M., Streib, J., Wong, C., Gallo, R. L., and Leung, D. Y. (2005) Interleukin-10 downregulates anti-microbial peptide expression in atopic dermatitis. J. Invest. Dermatol. 125, 738-745
Giannini, S. L., Al-Saleh, W., Piron, H., Jacobs, N., Doyen, J., Boniver, J., and Delvenne, P. (1998) Cytokine expression in sqamous intraepithelial lesions of the uterine cervix: implications for the generation of local immunosuppression. Clin. Exp. Immunol. 113, 183-189
Masson, V., de la Ballina, L. R., Munaut, C., Wielockx, B., Jost, M., Maillard, C., Blacher, S., Bajou, K., Itoh, T., Itohara, S., et al. (2005) Contribution of host MMP-2 and MMP-9 to promote tumor vascularization and invasion of malignant keratinocytes. FASEB J. 19, 234-236
Matthews, K., Leong, C. M., Baxter, L., Inglis, E., Yun, K., Backstrom, B. T., Doorbar, J., and Hibma, M. (2003) Depletion of Langerhans cells in human papillomavirus type 16-infected skin is associated with E6-mediated down regulation of E-cadherin. J. Virol. 77, 8378-8385
Grutkoski, P. S., Graeber, C. T., Lim, Y. P., Ayala, A., and Simms, H. H. (2003) Alpha-defensin 1 (human neutrophil protein 1) as an antichemotactic agent for human polymorphonuclear leukocytes. Antimicrob. Agents. Chemother. 47, 2666-2668
Van Wetering, S., Mannesse-Lazeroms, S. P., van Sterkenburg, M. A., and Hiemstra, P. S. (2002) Neutrophil defensins stimulate the release of cytokines by airway epithelial cells: modulation by dexamethasone. Inflamm. Res. 51, 8-15
Lundy, F. T., Orr, D. F., Gallagher, J. R., Maxwell, P., Shaw, C., Napier, S. S., Gerald Cowan, C., Lamey, P. J., and Marley, J. J. (2004) Identification and overexpression of human neutrophil alpha-defensins (human neutrophil peptides 1, 2 and 3) in squamous cell carcinomas of the human tongue. Oral. Oncol. 40, 139-144
Mizukawa, N., Sugiyama, K., Kamio, M., Yamachika, E., Ueno, T., Fukunaga, J., Takagi, S., and Sugahara, T. (2000) Immunohistochemical staining of human alpha-defensin-1 (HNP-1), in the submandibular glands of patients with oral carcinomas. Anticancer. Res. 20, 1125-1127
Lillard, J. W. J., Boyaka, P. N., Chertov, O., Oppenheim, J. J., and McGhee, J. R. (1999) Mechanisms for induction of acquired host immunity by neutrophil peptide defensins. Proc. Natl. Acad. Sci. U. S. A. 96, 651-656
Conejo-Garcia, J. R., Benencia, F., Courreges, M. C., Kang, E., Mohamed-Hadley, A., Buckanovich, R. J., Holtz, D. O., Jenkins, A., Na, H., Zhang, L., et al. (2004) Tumor-infiltrating dendritic cell precursors recruited by a beta-defensin contribute to vasculogenesis under the influence of Vegf-A. Nat. Med. 10, 950 -958
Chavakis, T., Cines, D. B., Rhee, J. S., Liang, O. D., Schubert, U., Hammes, H. P., Higazi, A. A., Nawroth, P. P., Preissner, K. T., and Bdeir, K. (2004) Regulation of neovascularization by human neutrophil peptides (alpha-defensins): a link between inflammation and angiogenesis. FASEB J. 18, 1306-1308
Economopoulou, M., Bdeir, K., Cines, D. B., Fogt, F., Bdeir, Y., Lubkowski, J., Lu, W., Preissner, K. T., Hammes, H. P., and Chavakis, T. (2005) Inhibition of pathologic retinal neovascularization by alpha-defensins. Blood. 106, 3831-3838
Muller, C. A., Markovic-Lipkovski, J., Klatt, T., Gamper, J., Schwarz, G., Beck, H., Deeg, M., Kalbacher, H., Widmann, S., Wessels, J. T., et al. (2002) Human alpha-defensins HNPs-1, -2, and -3 in renal cell carcinoma: influences on tumor cell proliferation. Am. J. Pathol. 160, 1311-1324
