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Zymosan by-passes the requirement for pulmonary antigen encounter in lung tissue-resident memory CD8 + T cell development
Mucosal Immunology ( IF 7.9 ) Pub Date : 2019-01-21 , DOI: 10.1038/s41385-018-0124-2
Irina Caminschi 1 , Mireille H Lahoud 1 , Angela Pizzolla 2 , Linda M Wakim 2
Affiliation  

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.



中文翻译:

酵母聚糖绕过肺组织驻留记忆 CD8 + T 细胞发育中肺抗原相遇的要求

肺中的组织驻留记忆 T 细胞 (Trm) 提供针对呼吸道病原体的前线防御。已经开发出将CD8 + Trm 群体寄宿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输送到气道中;一种必要的方法,因为局部同源抗原识别是最佳肺 Trm 发育所必需的。虽然抗原的肺部递送对于肺 Trm 发育很重要,但共同给予的佐剂对 Trm 分化的影响尚不清楚。我们表明,虽然改变与肺部递送抗原共同施用的佐剂不会影响肺 Trm 群体的大小,但当在没有抗原的情况下施用到气道中时,一种特定的佐剂酵母聚糖可以驱动效应子 CD8 +T 细胞分化为肺 Trm。通过 dectin-1 受体的酵母聚糖信号足以促进抗原非依赖性肺 Trm 发育。当与可注射的流感疫苗接种方案相结合时,鼻内酵母聚糖递送显着增加了流感病毒特异性肺 Trm 群体的大小。我们的结果强调,引发适当的局部炎症环境可以遵循肺部TRM发育中局部抗原识别的要求,并强调适当的辅助选择可以大大改善旨在引起肺部TRM的疫苗。

更新日期:2019-05-16
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