title: Local immunosuppression induced by high viral load of human papillomavirus: characterization of cellular phenotypes producing interleukin-10 in cervical neoplastic lesions.
abstract: A specific immune response to human papillomavirus (HPV) in the cervical microenvironment plays a key role in eradicating infection and eliminating mutated cells. However, high-risk HPVs modulate immune cells to create an immunosuppressive microenvironment, and induce these immune cells to produce interleukin 10 (IL-10). This production of IL-10, in conjunction with HPV infection, contributes to the appearance of cervical neoplastic lesions. We sought to characterize the IL-10-producing cellular phenotype, and investigate the influence of host and HPV factors upon the induction of an immunosuppressive microenvironment. Immunohistochemical analysis demonstrated an increase in IL-10 production by keratinocytes, macrophages and Langerhans cells in high-grade cervical lesions and cervical cancer. This increase was more pronounced in patients older than 30 years, and was also correlated with high viral load, and infection with a single HPV type, particularly high-risk HPVs. Our results indicate the existence of a highly immunosuppressive microenvironment composed of different IL-10-producing cellular phenotypes in cervical cancer samples, and samples classified as high-grade cervical lesions (cervical intraepithelial neoplasia stages II and III). The immunosuppressive microenvironment that developed for these different cellular phenotypes favours viral persistence and neoplastic progression.
authors.affiliation: Postgraduate Programme of Infectious and Parasitic Diseases, School of Medicine, Federal University of Mato Grosso do Sul, Campo Grande, Brazil.
authors.forename: Thiago Theodoro Martins
authors.initials: TT
authors.lastname: Prata
authors.affiliation: Centre for Biological and Health Sciences, Federal University of Mato Grosso do Sul, Campo Grande, Brazil.
authors.forename: Camila Mareti
authors.initials: CM
authors.lastname: Bonin
authors.affiliation: Centre for Biological and Health Sciences, Federal University of Mato Grosso do Sul, Campo Grande, Brazil.
authors.forename: Alda Maria Teixeira
authors.initials: AM
authors.lastname: Ferreira
authors.affiliation: Centre for Biological and Health Sciences, Federal University of Mato Grosso do Sul, Campo Grande, Brazil.
authors.forename: Cacilda Tezelli Junqueira
authors.initials: CT
authors.lastname: Padovani
authors.affiliation: Centre for Biological and Health Sciences, Federal University of Mato Grosso do Sul, Campo Grande, Brazil.
authors.forename: Carlos Eurico dos Santos
authors.initials: CE
authors.lastname: Fernandes
authors.affiliation: Multicentre Postgraduate Programme in Biochemistry and Molecular Biology, Federal University of Mato Grosso do Sul, Campo Grande, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Machado
authors.affiliation: School of Medicine, Federal University of Mato Grosso do Sul, Campo Grande, Brazil.
authors.forename: Inês Aparecida
authors.initials: IA
authors.lastname: Tozetti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology; D052161:Human papillomavirus 18 / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D015603:Keratinocytes / Q000378:metabolism; D007801:Langerhans Cells / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000276:immunology* / Q000821:virology; D059016:Tumor Microenvironment / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000821:virology; D019562:Viral Load; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000276:immunology* / Q000821:virology
chemical_list: C508609:IL10 protein, human; D016753:Interleukin-10
keywords: human papillomavirus; immunosuppression; interleukin-10