High-risk human papilloma virus infection decreases the frequency of dendritic Langerhans' cells in the human female genital tract.
Dendritic cells (DC) are often arranged in planar layers in tissues with high antigenic exposure, such as skin and mucosae. Providing an en face view, this arrangement optimizes in situ analysis regarding morphology (even of individual dendrites), topographic distribution (regular/clustered) and quantification. The few reports on human genital DC usually utilize single markers and conventional sections, restricting immunolabelling only to cell parts sectioned by the cut. To better assess DC in situ, we labelled epithelial sheets, prepared from fresh cervix biopsies, with antibodies to major histocompatibility complex (MHC)-CII, CD1a and Langerin, revealing (with each of these markers) a dense DC network in a planar-like, regular distribution. Using the hybrid capture system to detect the high-risk mucotropic human papilloma virus (HPV) group, 16 positive and five negative women were studied and the results were compared between these groups. DC frequency per area was substantially reduced (to approximately 50% for the three markers) in samples from all HPV-infected patients compared with samples from controls. Unlike HPV(-) samples, Langerin(+) DC in HPV(+) cervix exhibited a highly accentuated dendritic appearance. We believe this to be the first study using these three DC-restricted markers (Langerin, CD1a and MHC-CII) in cervical epithelial sheets from high-risk HPV(+) donors and also the first study to demonstrate the morphological and quantitative changes triggered by high-risk HPV infection. Cervical DC reduction in early, premalignant high-risk HPV infection might represent viral subversion strategies interfering with efficient antigen handling by the immune system's peripheral sentinels, the DC, perhaps hampering appropriate recruitment and subsequent development of effector (cytotoxic) T cells.
Jimenez-Flores
Rafael
R
Department of Experimental Pathology, CINVESTAV-IPN, Mexico.
Mendez-Cruz
Rene
R
Ojeda-Ortiz
Jorge
J
Muñoz-Molina
Rebeca
R
Balderas-Carrillo
Oscar
O
de la Luz Diaz-Soberanes
Maria
M
Lebecque
Serge
S
Saeland
Sem
S
Daneri-Navarro
Adrian
A
Garcia-Carranca
Alejandro
A
Ullrich
Stephen E
SE
Flores-Romo
Leopoldo
L
D036022:Capsid Proteins / Q000378:metabolism; D002584:Cervix Uteri / Q000033:anatomy & histology / Q000276:immunology* / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007124:Immunoenzyme Techniques; D007801:Langerhans Cells / Q000276:immunology*; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000473:pathology / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000473:pathology / Q000821:virology
D036022:Capsid Proteins; D006684:HLA-DR Antigens; D009856:Oncogene Proteins, Viral; C063317:L1 protein, Human papillomavirus type 16