Association between toll-like receptor expression and human papillomavirus type 16 persistence.

Association between toll-like receptor expression and human papillomavirus type 16 persistence.
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DOI:
10.1002/ijc.25400
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发表时间:
2011-02-15
影响因子:
6.4
通讯作者:
Moscicki, Anna-Barbara
Moscicki, Anna-Barbara
中科院分区:
医学1区
文献类型:
--
作者:
Daud, Ibrahim I.;Scott, Mark E.;Ma, Yifei;Shiboski, Stephen;Farhat, Sepideh;Moscicki, Anna-Barbara

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宫颈人乳头瘤病毒(HPV)感染的粘膜免疫控制机制仍不明确。由于Toll样受体(TLR)是先天免疫反应的关键参与者,我们研究了TLR表达与致癌HPV 16型或51型感染的年轻女性中病毒持续存在或清除之间的关系。在HPV感染的队列中,使用病毒采集前后收集的人宫颈内标本,通过定量逆转录-PCR测量TLR 1、TLR 2、TLR 3、TLR 4、TLR 6、TLR 7、TLR 8和TLR 9的信使RNA表达。Wilcoxon秩和检验用于比较随后清除感染的妇女与未清除感染的妇女之间从感染前到事件感染的变化。清除的HPV 16感染与病毒获得后四种病毒核酸敏感TLR(TLR 3、TLR 7、TLR 8和TLR 9)以及TLR 2的表达增加显著相关(P < 0.05)。对于HPV 51没有观察到类似的关联。在随后清除HPV 16感染的女性中,通过宫颈灌洗液标本的免疫测定,在发病前和发病访视之间TLR 1、TLR 3、TLR 7和TLR 8表达水平的变化与干扰素-α2水平的平行变化显著相关。这项研究表明,宫颈粘膜中TLR表达减弱是HPV 16干扰先天免疫应答的一种类型特异性机制,有助于病毒持续存在,TLR上调和由此产生的细胞因子诱导在随后的病毒清除中很重要。
The mechanisms involved in mucosal immune control of cervical human papillomavirus (HPV) infection remain ill-defined. Because Toll-like receptors (TLRs) are key players in innate immune responses, we investigated the association between TLR expression and viral persistence or clearance in young women with incident infections with oncogenic HPV types 16 or 51. Messenger RNA expression of TLR1, TLR2, TLR3, TLR4, TLR6, TLR7, TLR8, and TLR9 was measured by quantitative reverse transcription-PCR using human endocervical specimens, collected before and following viral acquisition, in a cohort well characterized for HPV infections. Wilcoxon rank sum test was used to compare the change seen from pre-infection to incident infection between women who subsequently cleared infection with those who did not. HPV 16 infections that cleared were significantly (P < 0.05) associated with an increase in expression of the four viral nucleic acid-sensing TLRs (TLR3, TLR7, TLR8 and TLR9) as well as TLR2 upon viral acquisition. Similar associations were not observed for HPV 51. In women who subsequently cleared their HPV 16 infection, changes in TLR1, TLR3, TLR7, and TLR8 expression levels between pre-incident and incident visits were significantly correlated with parallel changes in the levels of interferon-α2, measured by immunoassay in cervical lavage specimens. This study suggests that dampened TLR expression in the cervical mucosa is a type-specific mechanism by which HPV 16 interferes with innate immune responses, contributing to viral persistence, and that TLR upregulation and resultant cytokine induction is important in subsequent viral clearance.
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发表时间: 2003-02-01
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