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-3alpha production.
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 3alpha (MIP-3alpha), 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-3alpha 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-3alpha 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.
Guess
Jennifer C
JC
Department of Microbiology and Immunology, University of Rochester, New York 14642, USA.
McCance
Dennis J
DJ
D002460:Cell Line; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000378:metabolism / Q000502:physiology*; D015536:Down-Regulation; D015870:Gene Expression; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000821:virology; D007801:Langerhans Cells / Q000502:physiology*; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins / Q000502:physiology*
C108355:CCL20 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; C068651:E6 protein, Human papillomavirus type 16; D019402:Macrophage Inflammatory Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16