title: TLR9 is expressed in human papillomavirus-positive cervical cells and is overexpressed in persistent infections.
abstract: Control of human papillomavirus (HPV) infection involves the activation of Toll-like receptors (TLRs), key components of the mucosal antiviral response. Available studies on TLR expression in HPV-positive cervical cells are limited and reported conflicting results. This study quantified TLR 2, 3, 4, 7 and 9 transcripts in low-risk (LR) and high-risk (HR) HPV-positive and HPV-negative cervical samples from 154 women attending a gynaecological clinic. Expression levels of TLR 2, 3, 4 and 7 did not differ among samples, whereas TLR9 levels were quite significantly higher in LR and marginally significant in HR HPV-positive samples, with respect to the HPV-negative samples. Interestingly, in a subgroup of women with documented previous HPV-infection, TLR9 levels were extremely higher in patients persistently positive to the same HPV genotype for more than 1 year, with respect to women who cleared HPV infection and to those re-infected with a different genotype. These findings implicate TLR9 in the response to LR and HR HPVs, including HPV 16 known to interfere with TLR9 transcription in cell lines. Elevated TLR9 levels without HPV clearance in persistently infected women could drive inflammation thereby contributing to cervical cancer risk.
authors.affiliation: Virology Laboratory, Department of Molecular Medicine, Sapienza University, Viale di Porta Tiburtina 28, 00185 Rome, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Cannella
authors.affiliation: Virology Laboratory, Department of Molecular Medicine, Sapienza University, Viale di Porta Tiburtina 28, 00185 Rome, Italy. Electronic address: alessandra.pierangeli@uniroma1.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pierangeli
authors.affiliation: Virology Laboratory, Department of Molecular Medicine, Sapienza University, Viale di Porta Tiburtina 28, 00185 Rome, Italy.
authors.forename: Carolina
authors.initials: C
authors.lastname: Scagnolari
authors.affiliation: Virology Laboratory, Department of Molecular Medicine, Sapienza University, Viale di Porta Tiburtina 28, 00185 Rome, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Cacciotti
authors.affiliation: Virology Laboratory, Department of Molecular Medicine, Sapienza University, Viale di Porta Tiburtina 28, 00185 Rome, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Tranquilli
authors.affiliation: Department of Obstetric and Gynaecological Sciences and Urologic Sciences, Sapienza University, Viale del Policlinico 155, 00161 Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Stentella
authors.affiliation: Department of Obstetric and Gynaecological Sciences and Urologic Sciences, Sapienza University, Viale del Policlinico 155, 00161 Rome, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Recine
authors.affiliation: Virology Laboratory, Department of Molecular Medicine, Sapienza University, Viale di Porta Tiburtina 28, 00185 Rome, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Antonelli
mesh_terms: D000328:Adult; D000368:Aged; D002584:Cervix Uteri / Q000166:cytology* / Q000276:immunology* / Q000821:virology; D003430:Cross-Sectional Studies; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000276:immunology* / Q000821:virology; D012306:Risk; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis; D051196:Toll-Like Receptor 3 / Q000096:biosynthesis; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis; D051199:Toll-Like Receptor 7 / Q000096:biosynthesis; D051217:Toll-Like Receptor 9 / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: C495342:TLR2 protein, human; C495344:TLR3 protein, human; C495345:TLR4 protein, human; C495348:TLR7 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9
keywords: Cervical cancer; Human papillomavirus; Persistent infection; TLR9; Toll-like receptors