p53 serves as a host antiviral factor that enhances innate and adaptive immune responses to influenza A virus.
p53 serves as a host antiviral factor that enhances innate and adaptive immune responses to influenza A virus.
复制标题
DOI：
10.4049/jimmunol.1101459
复制
发表时间：
2011-12-15
期刊：
影响因子：
--
通讯作者：
Aaronson SA
中科院分区：
文献类型：
--
作者：
Muñoz-Fontela C;Pazos M;Delgado I;Murk W;Mungamuri SK;Lee SW;García-Sastre A;Moran TM;Aaronson SA
p53肿瘤抑制因子的几个直接靶基因已经在参与病毒传感、细胞因子产生和炎症的途径内被鉴定，这表明p53在抗病毒免疫中的潜在作用。越来越需要鉴定免疫因子以设计针对大流行性甲型流感病毒（IAV）的宿主靶向疗法，这促使我们研究内源性wt p53在对IAV的免疫应答中的作用。我们观察到p53的缺失导致肺和骨髓中细胞因子和抗病毒基因应答延迟，树突状细胞（DC）活化减少，IAV特异性CD 8 + T细胞免疫减少。因此，与野生型小鼠相比，p53−/−小鼠表现出更严重的IAV诱导的疾病。这些发现证实p53影响对IAV的抗病毒反应，影响先天性和适应性免疫。因此，除了作为肿瘤抑制基因的既定功能外，p53还作为IAV宿主抗病毒因子，可以对其进行调节以改善抗IAV治疗和疫苗。
Several direct target genes of the p53 tumor suppressor have been identified within pathways involved in viral sensing, cytokine production, and inflammation, suggesting a potential role of p53 in antiviral immunity. The increasing need to identify immune factors to devise host-targeted therapies against pandemic influenza A virus (IAV), led us to investigate the role of endogenous wt p53 on the immune response to IAV. We observed that the absence of p53, resulted in delayed cytokine and antiviral gene responses in lung and bone marrow, decreased dendritic cell (DC) activation and reduced IAV-specific CD8+ T cell immunity. Consequently, p53−/− mice showed a more severe IAV-induced disease compared to their wt counterparts. These findings establish that p53 influences the antiviral response to IAV, affecting both innate and adaptive immunity. Thus, in addition to its established functions as a tumor suppressor gene, p53 is serves as an IAV host antiviral factor that might be modulated to improve anti-IAV therapy and vaccines.
登录
查看更多内容
影响因子：
30.3
作者：
Hermesh T;Moltedo B;Moran TM;López CB
通讯作者：
López CB
DOI：
10.1073/pnas.1934678100
发表时间：
2003-09-16
影响因子：
11.1
作者：
Honda, K;Sakaguchi, S;Taniguchi, T
通讯作者：
Taniguchi, T
DOI：
10.1007/978-1-60761-421-0_24
发表时间：
2010-01-01
期刊：
DENDRITIC CELL PROTOCOLS, SECOND EDITION
影响因子：
--
作者：
Jakubzick, Claudia;Randolph, Gwendalyn J.
通讯作者：
Randolph, Gwendalyn J.
影响因子：
32.4
作者：
Kohlmeier JE;Cookenham T;Roberts AD;Miller SC;Woodland DL
通讯作者：
Woodland DL
影响因子：
4.4
作者：
Jenkins, Misty Rayna;Webby, Richard;Turner, Stephen J.
通讯作者：
Turner, Stephen J.