Poly(Anhydride) Nanoparticles Act as Active Th1 Adjuvants through Toll-Like Receptor Exploitation
Poly(Anhydride) Nanoparticles Act as Active Th1 Adjuvants through Toll-Like Receptor Exploitation
复制标题
DOI：
10.1128/cvi.00164-10
复制
发表时间：
2010-07
影响因子：
--
通讯作者：
I. Tamayo;J. Irache;Cristina Mansilla;Javier Ochoa-Repáraz;J. Lasarte;C. Gamazo
中科院分区：
文献类型：
--
作者：
I. Tamayo;J. Irache;Cristina Mansilla;Javier Ochoa-Repáraz;J. Lasarte;C. Gamazo
摘要：本文研究了聚甲基乙烯醚-共马来酸酐纳米颗粒（NPs）有效的th1佐剂能力的机制。传统上，聚合物NPs被认为是促进抗原和抗原呈递细胞（APCs）之间更密切相互作用的递送系统。我们的研究结果显示，多酸氢NPs还可以作为各种toll样受体（TLRs） （TLR2， -4和-5）的激动剂，触发th1型细胞因子释放（γ干扰素[IFN-γ]， 478 pg/ml，阴性对照组为39.6 pg/ml；白细胞介素12 [IL-12]， 40 pg/ml，阴性对照组为7.2 pg/ml），并且在与树突状细胞孵卵后，诱导CD54和CD86共刺激分子表达增加2.5至3.5倍。此外，体内研究表明，NPs积极引发CD8+ t细胞反应。空NPs免疫导致平均存活日期（攻毒后第7天至第23天）显著延迟，攻毒致死剂量血清型肠炎沙门氏菌后的保护水平为30%。综上所述，我们的研究结果更好地理解了NPs如何通过TLR开发在免疫预防和免疫治疗中作为活性Th1佐剂。
ABSTRACT The mechanisms that underlie the potent Th1-adjuvant capacity of poly(methyl vinyl ether-co-maleic anhydride) nanoparticles (NPs) were investigated. Traditionally, polymer NPs have been considered delivery systems that promote a closer interaction between antigen and antigen-presenting cells (APCs). Our results revealed that poly(anhydride) NPs also act as agonists of various Toll-like receptors (TLRs) (TLR2, -4, and -5), triggering a Th1-profile cytokine release (gamma interferon [IFN-γ], 478 pg/ml versus 39.6 pg/ml from negative control; interleukin-12 [IL-12], 40 pg/ml versus 7.2 pg/ml from negative control) and, after incubation with dendritic cells, inducing a 2.5- to 3.5-fold increase of CD54 and CD86 costimulatory molecule expression. Furthermore, in vivo studies suggest that NPs actively elicit a CD8+ T-cell response. Immunization with empty NPs resulted in a significant delay in the mean survival date (from day 7 until day 23 postchallenge) and a protection level of 30% after challenge against a lethal dose of Salmonellaenterica serovar Enteritidis. Taken together, our results provide a better understanding of how NPs act as active Th1 adjuvants in immunoprophylaxis and immunotherapy through TLR exploitation.