Zymosan by-passes the requirement for pulmonary antigen encounter in lung tissue-resident memory CD8+ T cell development
Zymosan by-passes the requirement for pulmonary antigen encounter in lung tissue-resident memory CD8+ T cell development
复制标题
DOI：
10.1038/s41385-018-0124-2
复制
发表时间：
2019-02-01
影响因子：
8
通讯作者：
Wakim, Linda M.
中科院分区：
文献类型：
--
作者：
Caminschi, Irina;Lahoud, Mireille H.;Wakim, Linda M.
组织驻留记忆T细胞（Trm）在肺提供一线防御呼吸道病原体。已经开发出将CD8(+) Trm群体放置在肺部的疫苗接种模型，所有这些模型都将抗原和佐剂局部递送到气道中；作为局部同源抗原识别的必要途径是最佳的肺Trm发展所必需的。尽管肺内抗原的传递对肺Trm的发展很重要，但联合佐剂对Trm分化的影响尚不清楚。我们发现，虽然改变与肺递送抗原共同给药的佐剂不会影响肺Trm群体的大小，但一种特殊的佐剂，zymosan，当没有抗原的情况下给药到气道中时，可以驱动效应CD8(+) T细胞分化为肺Trm。通过dectin-1受体的Zymosan信号传导足以促进抗原非依赖性肺Trm的发展。当与注射流感疫苗方案相结合时，经鼻给药显著增加了流感病毒特异性肺Trm群体的规模。我们的研究结果强调，在肺Trm的发展过程中，激发适当的局部炎症环境可以绕过对局部抗原识别的要求，并强调适当选择佐剂可以大大改善旨在引发肺Trm的疫苗。
Tissue-resident memory T cells (Trm) in the lung provide a frontline defence against respiratory pathogens. Vaccination models that lodge CD8(+) Trm populations in the lung have been developed, all of which incorporate the local delivery of antigen plus adjuvant into the airways; a necessary approach as local cognate antigen recognition is required for optimal lung Trm development. Although pulmonary delivery of antigen is important for lung Trm development, the impact the co-administered adjuvant has on Trm differentiation is unclear. We show that while altering the adjuvant co-administered with the pulmonary delivered antigen does not impact the size of the lung Trm population, a particular adjuvant, zymosan, when administered into the airways without antigen can drive effector CD8(+) T cells to differentiate into lung Trm. Zymosan signalling via dectin-1 receptor was sufficient to promote antigen-independent lung Trm development. When combined with an injectable influenza vaccination regime, intranasal zymosan delivery significantly boosted the size of the influenza virus-specific lung Trm population. Our results highlight that eliciting the appropriate local inflammatory milieu can by-pass the requirement for local antigen recognition in lung Trm development and emphasises that the appropriate selection of adjuvant can greatly improve vaccines that aim to elicit pulmonary Trm.