Human papillomavirus can escape immune recognition through Langerhans cell phosphoinositide 3-kinase activation
Human papillomavirus can escape immune recognition through Langerhans cell phosphoinositide 3-kinase activation
复制标题
DOI：
10.4049/jimmunol.174.11.7172
复制
发表时间：
2005-06-01
影响因子：
4.4
通讯作者：
Kast, WM
中科院分区：
文献类型：
--
作者：
Fausch, SC;Fahey, LM;Kast, WM
宫颈上皮人乳头瘤病毒(HPV)感染与宫颈癌的发生有关。虽然大多数感染HPV的妇女清除了她们的皮损，但从感染到消退的漫长潜伏期表明，HPV进化了免疫逃逸机制。树突状细胞是疫苗接种程序的靶点，与HPV病毒样颗粒孵育后可诱导HPV特异性免疫反应。位于初次感染部位的朗格汉斯细胞(LC)不会产生反应，暗示LC是HPV使用的一种免疫逃逸机制。与HPV病毒样颗粒孵育的LC上调PI3-K信号通路，下调MAPK信号通路。通过抑制PI3-K并与HPV病毒样颗粒孵育，LC启动了强大的HPV特异性反应。LC中PI3-K的激活定义了HPV的一种新的逃逸机制，抑制PI3-K可能成为增强HPV免疫的有效临床靶点。
Human papillomavirus (HPV) infection of cervical epithelium is linked to the generation of cervical cancer. Although most women infected with HPV clear their lesions, the long latency period from infection to resolution indicates that HPV evolved immune escape mechanisms. Dendritic cells, which are targeted by vaccination procedures, incubated with HPV virus-like particles induce an HPV-specific immune response. Langerhans cells (LC), which are located at the sites of primary infection, do not induce a response implicating the targeting of LC as an immune escape mechanism used by HPV. LC incubated with HPV virus-like particles up-regulate the phosphoinositide 3-kinase (PI3-K) pathway and down-regulate MAPK pathways. With the inhibition of PI3-K and incubation with HPV virus-like particles, LC initiate a potent HPV-specific response. PI3-K activation in LC defines a novel escape mechanism used by HPV, and PI3-K inhibition may serve as an effective clinical target to enhance HPV immunity.