Laboratory of Vaccine Research, Netherlands Vaccine Institute, Bilthoven, The Netherlands.
PLoS One. 2010 Dec 23;5(12):e15692. doi: 10.1371/journal.pone.0015692.
Neisseria meningitidis and Bordetella pertussis are Gram-negative bacterial pathogens that can cause serious diseases in humans. N. meningitidis outer membrane vesicle (OMV) vaccines and whole cell pertussis vaccines have been successfully used in humans to control infections with these pathogens. The mechanisms behind their effectiveness are poorly defined. Here we investigated the role of Toll-like receptor (TLR) 2 and TLR4 in the induction of immune responses in mice after immunization with these vaccines. Innate and adaptive immune responses were compared between wild type mice and mice deficient in TLR2, TLR4, or TRIF. TRIF-deficient and TLR4-deficient mice showed impaired immunity after immunization. In contrast, immune responses were not lower in TLR2-/- mice but tended even to be higher after immunization. Together our data demonstrate that TLR4 activation contributes to the immunogenicity of the N. meningitidis OMV vaccine and the whole cell pertussis vaccine, but that TLR2 activation is not required.
脑膜炎奈瑟菌和百日咳博德特氏菌是革兰氏阴性细菌病原体,可导致人类严重疾病。脑膜炎奈瑟菌外膜囊泡(OMV)疫苗和全细胞百日咳疫苗已成功用于人类控制这些病原体的感染。其有效性背后的机制尚未明确。在这里,我们研究了 Toll 样受体(TLR)2 和 TLR4 在接种这些疫苗后诱导小鼠免疫反应中的作用。在野生型小鼠和 TLR2、TLR4 或 TRIF 缺陷型小鼠之间比较了先天和适应性免疫反应。TRIF 缺陷型和 TLR4 缺陷型小鼠在免疫接种后免疫功能受损。相比之下,TLR2-/- 小鼠的免疫反应并没有降低,但在免疫接种后甚至有升高的趋势。总之,我们的数据表明 TLR4 激活有助于脑膜炎奈瑟菌 OMV 疫苗和全细胞百日咳疫苗的免疫原性,但 TLR2 激活不是必需的。