Primary nasal viral infection rewires the tissue-scale memory response.

IF 0.9 Q3 ENGINEERING, MULTIDISCIPLINARY
Samuel W Kazer, Colette Matysiak Match, Erica M Langan, Marie-Angèle Messou, Thomas J LaSalle, Elise O'Leary, Jessica Marbourg, Katherine Naughton, Ulrich H von Andrian, Jose Ordovas-Montanes
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引用次数: 0

Abstract

The nasal mucosa is frequently the initial site of respiratory viral infection, replication, and transmission. Recent work has started to clarify the independent responses of epithelial, myeloid, and lymphoid cells to viral infection in the nasal mucosa, but their spatiotemporal coordination and relative contributions remain unclear. Furthermore, understanding whether and how primary infection shapes tissue-scale memory responses to secondary challenge is critical for the rational design of nasal-targeting therapeutics and vaccines. Here, we generated a single-cell RNA-sequencing (scRNA-seq) atlas of the murine nasal mucosa sampling three distinct regions before and during primary and secondary influenza infection. Primary infection was largely restricted to respiratory mucosa and induced stepwise changes in cell type, subset, and state composition over time. Type I Interferon (IFN)-responsive neutrophils appeared 2 days post infection (dpi) and preceded transient IFN-responsive/cycling epithelial cell responses 5 dpi, which coincided with broader antiviral monocyte and NK cell accumulation. By 8 dpi, monocyte-derived macrophages (MDMs) expressing Cxcl9 and Cxcl16 arose alongside effector cytotoxic CD8 and Ifng-expressing CD4 T cells. Following viral clearance (14 dpi), rare, previously undescribed Krt13+ nasal immune-interacting floor epithelial (KNIIFE) cells expressing multiple genes with immune communication potential increased concurrently with tissue-resident memory T (TRM)-like cells and early IgG+/IgA+ plasmablasts. Proportionality analysis coupled with cell-cell communication inference, alongside validation by in situ microscopy, underscored the CXCL16-CXCR6 signaling axis between MDMs and effector CD8 T cells 8dpi and KNIIFE cells and TRM cells 14 dpi. Secondary influenza challenge with a homologous or heterologous strain administered 60 dpi induced an accelerated and coordinated myeloid and lymphoid response without epithelial proliferation, illustrating how tissue-scale memory to natural infection engages both myeloid and lymphoid cells to reduce epithelial regenerative burden. Together, this atlas serves as a reference for viral infection in the upper respiratory tract and highlights the efficacy of local coordinated memory responses upon rechallenge.

原发性鼻腔病毒感染重塑了组织规模记忆反应。
鼻黏膜经常是呼吸道病毒感染、复制和传播的最初部位。最近的研究已开始阐明鼻黏膜上皮细胞、骨髓细胞和淋巴细胞对病毒感染的独立反应,但它们之间的时空协调和相对贡献仍不清楚。此外,了解原发性感染是否以及如何形成对继发性挑战的组织规模记忆反应,对于合理设计鼻腔靶向疗法和疫苗至关重要。在这里,我们生成了小鼠鼻粘膜的单细胞 RNA 序列(scRNA-seq)图谱,在原发性和继发性流感感染之前和期间对三个不同区域进行了采样。原发性感染主要局限于呼吸道粘膜,并随着时间的推移诱导细胞类型、亚群和状态组成的逐步变化。I型干扰素(IFN)反应性中性粒细胞在感染后2天(dpi)出现,5 dpi之前出现短暂的IFN反应性/循环上皮细胞反应,这与更广泛的抗病毒单核细胞和NK细胞聚集相吻合。到 8 dpi 时,表达 Cxcl9 和 Cxcl16 的单核细胞衍生巨噬细胞(MDMs)与表达细胞毒性 CD8 和 Ifng 的 CD4 T 细胞同时出现。病毒清除后(14 dpi),罕见的、以前未描述过的表达具有免疫通讯潜能的多个基因的 K rt13+ n asal i mmune- i nteracting f loor e pithelial(KNIIFE)细胞与组织驻留记忆 T(TRM)样细胞和早期 IgG+/IgA+ 浆细胞同时增加。比例分析结合细胞-细胞通讯推断以及原位显微镜验证,强调了 MDMs 和效应 CD8 T 细胞 8 dpi 以及 KNIIFE 细胞和 TRM 细胞 14 dpi 之间的 CXCL16-CXCR6 信号轴。用同源或异源菌株在 60 dpi 进行二次流感挑战,可诱导加速和协调的髓细胞和淋巴细胞反应,而不会导致上皮细胞增殖,这说明了对自然感染的组织规模记忆是如何调动髓细胞和淋巴细胞以减少上皮细胞再生负担的。总之,该图谱可作为上呼吸道病毒感染的参考,并强调了局部协调记忆反应在再挑战时的功效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Failure Analysis and Prevention
Journal of Failure Analysis and Prevention ENGINEERING, MULTIDISCIPLINARY-
CiteScore
2.00
自引率
8.30%
发文量
200
期刊介绍: The Journal of Failure Analysis and Prevention (JFAP) is written for and read by individuals involved in failure analysis, materials scientists, and mechanical, manufacturing, aeronautical, civil, chemical, corrosion, and design engineers. The publication is unique in that it contains current news and technical articles, as well as archival peer-reviewed papers and reviews. JFAP provides information gathering techniques, technical analysis, and emerging tools that will assist failure analysis professionals in determining the cause of failures and eliminating failures in the future. Articles demonstrate the importance of failure analysis to product/performance improvements and industrial problem solving. JFAP is intended to be of interest to both the experienced and less experienced failure analysis practitioner with a focus on shared interest across the industries.Bi-monthly periodical for the failure analyst. Provides practical information for determining the cause of failures and eliminating future failures. Highlights information-gathering techniques, technical analysis and emerging tools to assist the future analyst. Peer-reviewed articles demonstrate the important of failure analysis, product/performance improvement and industrial problem solving. Written for the experienced and less experienced failure analysis practitioner.
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