Nasal mucosal tissues are equipped with physical barriers, mucus and cilia, on their surface. The mucus layer captures inhaled materials, and the cilia remove the inhaled materials from the epithelial layer by asymmetrical beating. The effect of nasal physical barriers on the vaccine efficacy remains to be investigated. Tubulin tyrosine ligase-like family, member 1 (Ttll1) is an essential enzyme for appropriate movement of the cilia on respiratory epithelium, and its deficiency (Ttll1-KO) leads to mucus accumulation in the nasal cavity. Here, when mice were intra-nasally immunized with pneumococcal surface protein A (PspA, as vaccine antigen) together with cholera toxin (CT, as mucosal adjuvant), Ttll1-KO mice showed higher levels of PspA-specific IgA in the nasal wash and increased numbers of PspA-specific IgA-producing plasma cells in the nasal passages when compared with Ttll1 hetero (He) mice. Mucus removal by N-acetylcysteine did not affect the enhanced immune responses in Ttll1-KO mice versus Ttll1-He mice. Immunohistological and flow cytometry analyses revealed that retention time of PspA in the nasal cavity in Ttll1-KO mice was longer than that in Ttll1-He mice. Consistently, uptake of PspA by dendritic cells was higher in the nasopharynx-associated lymphoid tissue (NALT) of Ttll1-KO mice than that of Ttll1-He mice. These results indicate that the ciliary function of removing vaccine antigen from the NALT epithelial layer is a critical determinant of the efficacy of nasal vaccine.

中文翻译：

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粘膜纤毛运动受损可增强针对霍乱毒素鼻疫苗的抗原特异性鼻 IgA 免疫反应。


鼻粘膜组织表面具有物理屏障、粘液和纤毛。粘液层捕获吸入物质，纤毛通过不对称拍打将吸入物质从上皮层去除。鼻物理屏障对疫苗功效的影响仍有待研究。微管蛋白酪氨酸连接酶样家族成员 1 (Ttll1) 是呼吸道上皮纤毛适当运动所必需的酶，其缺陷 (Ttll1-KO) 会导致鼻腔内粘液积聚。在这里，当小鼠用肺炎球菌表面蛋白 A（PspA，作为疫苗抗原）和霍乱毒素（CT，作为粘膜佐剂）一起进行鼻内免疫时，Ttll1-KO 小鼠在鼻洗液和鼻洗液中表现出较高水平的 PspA 特异性 IgA。与 Ttll1 异种 (He) 小鼠相比，鼻道中产生 PspA 特异性 IgA 的浆细胞数量增加。 N-乙酰半胱氨酸去除粘液并不影响 Ttll1-KO 小鼠与 Ttll1-He 小鼠相比增强的免疫反应。免疫组织学和流式细胞术分析显示，Ttll1-KO 小鼠鼻腔中 PspA 的保留时间比 Ttll1-He 小鼠长。一致地，Ttll1-KO 小鼠的鼻咽相关淋巴组织 (NALT) 中树突状细胞对 PspA 的摄取高于 Ttll1-He 小鼠。这些结果表明，从 NALT 上皮层去除疫苗抗原的纤毛功能是鼻疫苗功效的关键决定因素。