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However, it remains unclear which immune cells are implicated in this process and no study has evaluated the direct interaction between HPVs and NK cells, a key player in host resistance to viruses and tumors. We demonstrated an NK\u2010cell infiltration in HPV\u2010associated preneoplastic cervical lesions. Since HPVs cannot grow in vitro, virus\u2010like particles (VLPs) were used as a model for studying the NK\u2010cell response against the virus. Interestingly, NK cells displayed higher cytotoxic activity and cytokine production (TNF\u2010\u03b1 and IFN\u2010\u03b3) in the presence of HPV\u2010VLPs. Using flow cytometry and microscopy, we observed that NK\u2010cell stimulation was linked to rapid VLP entry into these cells by macropinocytosis. Using CD16<jats:sup>+<\/jats:sup> and CD16<jats:sup>\u2212<\/jats:sup> NK\u2010cell lines and a CD16\u2010blocking antibody, we demonstrated that CD16 is necessary for HPV\u2013VLP internalization, as well as for degranulation and cytokine production. Thus, we show for the first time that NK cells interact with HPVs and can participate in the immune response against HPV\u2010induced lesions.<\/jats:p>","DOI":"10.1002\/eji.201141693","type":"journal-article","created":{"date-parts":[[2011,8,10]],"date-time":"2011-08-10T09:32:25Z","timestamp":1312968745000},"page":"3240-3252","source":"Crossref","is-referenced-by-count":36,"title":["Human papillomavirus entry into NK cells requires CD16 expression and triggers cytotoxic activity and cytokine secretion"],"prefix":"10.1002","volume":"41","author":[{"given":"Virginie M.","family":"Renoux","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bettina","family":"Bisig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inge","family":"Langers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estelle","family":"Dortu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e9atrice","family":"Cl\u00e9menceau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Thiry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christophe","family":"Deroanne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain","family":"Colige","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques","family":"Boniver","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Delvenne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,9,27]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2008.11.046"},{"key":"e_1_2_6_3_2","first-page":"C1","article-title":"HPV and cervical cancer in the world, 2007 Report","volume":"25","author":"Castellsagu\u00e9 X.","year":"2007","journal-title":"Vaccine"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.6.7.1131"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1994.tb06778.x"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2007.03.049"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60946-5"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.28.2186"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/516784"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3281c61201"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni0211-107"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.267"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609692104"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/383041b0"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2803"},{"key":"e_1_2_6_16_2","doi-asserted-by":"crossref","first-page":"180","DOI":"10.4049\/jimmunol.133.1.180","article-title":"The Fc receptor for IgG on human natural killer cells: phenotypic, functional, and comparative studies with monoclonal antibodies","volume":"133","author":"Perussia B. 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