The role of Toll-like receptor 4 in eliciting acquired immune responses against nontypeable Haemophilus influenzae following intranasal immunization with outer membrane protein
The role of Toll-like receptor 4 in eliciting acquired immune responses against nontypeable Haemophilus influenzae following intranasal immunization with outer membrane protein
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DOI：
10.1016/j.ijporl.2009.08.015
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发表时间：
2009-12-01
影响因子：
1.5
通讯作者：
Suzuki, Masashi
中科院分区：
文献类型：
--
作者：
Hirano, Takashi;Kodama, Satoru;Suzuki, Masashi
【摘要】：目的:急性中耳炎(AOM)是儿童最常见的传染病之一。不可分型流感嗜血杆菌 (NTHi) 被认为是 AOM 的主要病原体。目前的治疗方案主要依赖于抗生素的使用，因此开发疫苗来预防这种疾病是公共卫生的紧迫目标。外膜蛋白 (OMP) 是 NTHi 疫苗接种的有希望的候选靶点。方法：我们使用 C3H/HeJ（Toll 样受体 4 [TLR4] 突变体）小鼠，该小鼠自发产生并具有非功能性 TLR4 蛋白，以及正常野生型 (WT) C3H/HeN 小鼠。这些小鼠使用 NTHi 的 OMP 进行鼻内免疫，以研究通过 TLR4 获得性免疫的机制。我们检测了两种品系在鼻内免疫过程中粘膜和全身抗体分泌的动力学以及产生抗体的淋巴细胞向粘膜的迁移。结果：在TLR4突变型和WT小鼠中均引发了针对来自NTHi的OMP的粘膜和全身免疫应答。然而，WT 小鼠的粘膜 IgA、全身 IgG 和 Th1 免疫反应强于 TLR4 突变小鼠。结论：TLR4 在 Th1 功能中发挥着重要作用，对于鼻内施用 OMP 的获得性免疫反应的最佳发展至关重要。在预防 AOM 的个体疫苗接种中需要考虑通过 TLR4 表达产生的各种免疫反应。 (C) 2009 Elsevier Ireland Ltd. 保留所有权利。
Objective: Acute otitis media (AOM) is one of the most common infectious diseases in children. Nontypeable Haemophilus influenzae (NTHi) is considered a major pathogen in AOM. Current treatment options depend mainly on the use of antibiotics, thus developing vaccines to prevent this disease is an urgent goal for public health. Outer membrane proteins (OMPs) are promising candidate targets for vaccination against NTHi.Methods: We used C3H/HeJ (Toll-like receptor 4 [TLR4]-mutant) mice, which arose spontaneously and have a non-functional TLR4 protein, and normal wild-type (WT) C3H/HeN mice. These mice were immunized intranasally with OMP from NTHi to investigate the mechanism of acquired immunity via TLR4. We examined the kinetics of mucosal and systemic antibody secretion and the migration of antibody producing lymphocytes to the mucosa in both strains during the course of intranasal immunization.Results: The mucosal and systemic immune responses against OMP from NTHi were elicited in both TLR4-mutant and WT mice. However, the mucosal IgA, and systemic IgG, and Th1 immune responses in WT mice were stronger than those in TLR4-mutant mice.Conclusions: TLR4 plays an important role in relation to Th1 function for optimal development of the acquired immune responses to OMP administered intranasally. The variety of immune responses via TLR4 expression needs to be taken into consideration of individual vaccinations to prevent AOM. (C) 2009 Elsevier Ireland Ltd. All rights reserved.