Antigen discovery unveils resident memory and migratory cell roles in antifungal resistance.,Mucosal Immunology

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Antigen discovery unveils resident memory and migratory cell roles in antifungal resistance.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2020-01-03 , DOI: 10.1038/s41385-019-0244-3
Hannah E Dobson ₁ , Lucas Dos Santos Dias ₁ , Elaine M Kohn ₁ , Scott Fites ₁ , Darin L Wiesner ₁ , Thamotharampillai Dileepan ₂ , Gregory C Kujoth ₁ , Ambily Abraham ₃ , Gary R Ostroff ₃ , Bruce S Klein _{1,

4,

5} , Marcel Wüthrich ₁

Affiliation

Priming at the site of natural infection typically elicits a protective T cell response against subsequent pathogen encounter. Here, we report the identification of a novel fungal antigen that we harnessed for mucosal vaccination and tetramer generation to test whether we can elicit protective, antigen-specific tissue-resident memory (Trm) CD4+ T cells in the lung parenchyma. In contrast to expectations, CD69+, CXCR3+, CD103- Trm cells failed to protect against a lethal pulmonary fungal infection. Surprisingly, systemic vaccination induced a population of tetramer+ CD4+ T cells enriched within the pulmonary vasculature, and expressing CXCR3 and CX3CR1, that migrated to the lung tissue upon challenge and efficiently protected mice against infection. Mucosal vaccine priming of Trm may not reliably protect against mucosal pathogens.

中文翻译：

抗原的发现揭示了驻留记忆和迁移细胞在抗真菌耐药性中的作用。

在自然感染部位启动通常会引发保护性 T 细胞反应，以抵抗随后遇到的病原体。在这里，我们报告了一种新型真菌抗原的鉴定，我们利用该抗原进行粘膜疫苗接种和四聚体生成，以测试我们是否可以在肺实质中引发保护性抗原特异性组织驻留记忆（Trm）CD4+T细胞。与预期相反，CD69+、CXCR3+、CD103-Trm 细胞未能防止致命的肺部真菌感染。令人惊讶的是，全身疫苗接种诱导了肺血管系统内富集的四聚体+ CD4+ T 细胞群，并表达 CXCR3 和 CX3CR1，这些细胞在受到攻击后迁移到肺组织，并有效保护小鼠免受感染。 Trm 粘膜疫苗引发可能无法可靠地预防粘膜病原体。

更新日期：2020-01-03

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