Abstract:
:Human papillomavirus (HPV) infections account for more than 50% of infection-linked cancers in women worldwide. The immune system controls, at least partially, viral infection and around 90% of HPV-infected women clear the virus within two years. 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-cell infiltration in HPV-associated preneoplastic cervical lesions. Since HPVs cannot grow in vitro, virus-like particles (VLPs) were used as a model for studying the NK-cell response against the virus. Interestingly, NK cells displayed higher cytotoxic activity and cytokine production (TNF-α and IFN-γ) in the presence of HPV-VLPs. Using flow cytometry and microscopy, we observed that NK-cell stimulation was linked to rapid VLP entry into these cells by macropinocytosis. Using CD16(+) and CD16(-) NK-cell lines and a CD16-blocking antibody, we demonstrated that CD16 is necessary for HPV-VLP 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-induced lesions.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Renoux VM,Bisig B,Langers I,Dortu E,Clémenceau B,Thiry M,Deroanne C,Colige A,Boniver J,Delvenne P,Jacobs Ndoi
10.1002/eji.201141693subject
Has Abstractpub_date
2011-11-01 00:00:00pages
3240-52issue
11eissn
0014-2980issn
1521-4141journal_volume
41pub_type
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