Decreased migration of Langerhans precursor-like cells in response to human keratinocytes expressing human papillomavirus type 16 E6/E7 is related to reduced macrophage inflammatory protein-3α production

被引:114
作者
Guess, JC
McCance, DJ
机构
[1] Univ Rochester, Dept Microbiol & Immunol, Rochester, NY 14642 USA
[2] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY 14642 USA
关键词
D O I
10.1128/JVI.79.23.14852-14862.2005
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Infection with high-risk human papillomavirus (HPV) types, particularly types 16 and 18, contributes to 90% of cervical cancer cases. HPV infects cutaneous or mucosal epithelium, tissue that is monitored for microbial infection or damage by Langerhans cells. In lesions produced by HPV type 16, there is a reduction in numbers of immune cells, especially Langerhans cells. Langerhans precursor cells selectively express CCR6, the receptor for macrophage inflammatory protein 3 alpha (MIP-3 alpha), and function as potent immune responders to inflamed epithelium and initiators of the innate immune response. It has been reported that E6 and E7 of high-risk HPVs interfere with immune mediators in order to suppress the recruitment of immune cells and antiviral activities of infected cells. Here we show that, following proinflammatory stimulus, HPV-16 E6 and E7 inhibit MIP-3 alpha transcription, resulting in suppression of the migration of immature Langerhans precursor-like cells. Interestingly, the E6 and E7 proteins from the low-risk HPV types also inhibited MIP-3 alpha transcription. These results suggest that one mechanism by which HPV-infected cells suppress the immune response may be through the inhibition of a vital alert signal, thus contributing to the persistence of HPV infection.
引用
收藏
页码:14852 / 14862
页数:11
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