小鼠呼吸道病毒感染后的上皮记忆导致抗原呈递的延长增强
2025/08/31
摘要
背景：病毒性下呼吸道感染（LRTI）可以降低随后LRTI的严重程度，但也与呼吸道过敏的发展和恶化有关。在这里，我们显示病毒LRTI可以印记肺上皮细胞（LEC），导致延长的表型和功能变化。
方法：通过鼻内施用呼吸道合胞病毒（RSV）感染小鼠。28天后，使用冷分散酶消化分离LEC，然后进行磁激活细胞分选。使用靶标下的切割和使用核酸酶（切割和运行）的释放来评估表观遗传变化，而使用NanoString和qPCR评估转录变化。流式细胞术用于测量抗原呈递后细胞表面主要组织相容性复合物（MHC）水平，抗原摄取和加工速率以及OT-I细胞增殖。
结果：我们在RSV感染后28天鉴定了小鼠LEC的表观遗传和转录组学变化，特别是影响与MHC相关的基因。体内LPS刺激后，MHC-I和MHC-Ⅱ的持续上调进一步增加。重要的是，MHC上调与抗原摄取和加工增加以及对T细胞的抗原呈递增加有关。
结论：我们的数据表明，RSV可以诱导LEC延长抗原呈递的上调，有可能促进局部T细胞对微生物抗原和过敏原的反应，并增强免疫力或易感宿主的呼吸道过敏。
Piotr P Janas, Wouter T'Jonck, Matthew O Burgess, Maximilian Reck, Caroline Chauché, Matthieu Vermeren, Christopher D Lucas, Calum Bain, Robert Illingworth, Edward W Roberts, Henry J McSorley, Jürgen Schwarze
Abstract
Background: Viral lower respiratory tract infections (LRTIs) can reduce the severity of subsequent LRTIs but have also been linked to respiratory allergy development and exacerbation. Here, we show that viral LRTI can imprint lung epithelial cells (LECs), leading to prolonged phenotypic and functional changes.
Methods: Mice were infected via intranasal administration of respiratory syncytial virus (RSV). After 28 days, LECs were isolated using cold dispase digestion followed by magnetic-activated cell sorting. Epigenetic changes were assessed using Cleavage Under Targets and Release Using Nuclease (CUT&RUN), while transcriptional changes were evaluated using NanoString and qPCR. Flow cytometry was employed to measure cell surface major histocompatibility complex (MHC) levels, antigen uptake and processing rates, and OT-I cell proliferation after antigen presentation.
Results: We identified epigenetic and transcriptomic changes in murine LECs 28 days after RSV infection, especially impacting genes associated with MHC. Lasting upregulation of MHC-I and MHC-II was further increased following in vivo LPS stimulation. Importantly, MHC upregulation was associated with increased antigen uptake and processing, as well as increased antigen presentation to T cells.
Conclusions: Our data demonstrate that RSV can induce prolonged upregulation of antigen presentation by LECs, with the potential to facilitate local T cell responses to microbial antigens and allergens and to enhance immunity or in susceptible hosts respiratory allergy.
背景：病毒性下呼吸道感染（LRTI）可以降低随后LRTI的严重程度，但也与呼吸道过敏的发展和恶化有关。在这里，我们显示病毒LRTI可以印记肺上皮细胞（LEC），导致延长的表型和功能变化。
方法：通过鼻内施用呼吸道合胞病毒（RSV）感染小鼠。28天后，使用冷分散酶消化分离LEC，然后进行磁激活细胞分选。使用靶标下的切割和使用核酸酶（切割和运行）的释放来评估表观遗传变化，而使用NanoString和qPCR评估转录变化。流式细胞术用于测量抗原呈递后细胞表面主要组织相容性复合物（MHC）水平，抗原摄取和加工速率以及OT-I细胞增殖。
结果：我们在RSV感染后28天鉴定了小鼠LEC的表观遗传和转录组学变化，特别是影响与MHC相关的基因。体内LPS刺激后，MHC-I和MHC-Ⅱ的持续上调进一步增加。重要的是，MHC上调与抗原摄取和加工增加以及对T细胞的抗原呈递增加有关。
结论：我们的数据表明，RSV可以诱导LEC延长抗原呈递的上调，有可能促进局部T细胞对微生物抗原和过敏原的反应，并增强免疫力或易感宿主的呼吸道过敏。
（中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校）
（Allergy. 2025 Aug 7. doi: 10.1111/all.16683.）
Epithelial Memory After Respiratory Viral Infection in Mice Results in Prolonged Enhancement of Antigen PresentationPiotr P Janas, Wouter T'Jonck, Matthew O Burgess, Maximilian Reck, Caroline Chauché, Matthieu Vermeren, Christopher D Lucas, Calum Bain, Robert Illingworth, Edward W Roberts, Henry J McSorley, Jürgen Schwarze
Abstract
Background: Viral lower respiratory tract infections (LRTIs) can reduce the severity of subsequent LRTIs but have also been linked to respiratory allergy development and exacerbation. Here, we show that viral LRTI can imprint lung epithelial cells (LECs), leading to prolonged phenotypic and functional changes.
Methods: Mice were infected via intranasal administration of respiratory syncytial virus (RSV). After 28 days, LECs were isolated using cold dispase digestion followed by magnetic-activated cell sorting. Epigenetic changes were assessed using Cleavage Under Targets and Release Using Nuclease (CUT&RUN), while transcriptional changes were evaluated using NanoString and qPCR. Flow cytometry was employed to measure cell surface major histocompatibility complex (MHC) levels, antigen uptake and processing rates, and OT-I cell proliferation after antigen presentation.
Results: We identified epigenetic and transcriptomic changes in murine LECs 28 days after RSV infection, especially impacting genes associated with MHC. Lasting upregulation of MHC-I and MHC-II was further increased following in vivo LPS stimulation. Importantly, MHC upregulation was associated with increased antigen uptake and processing, as well as increased antigen presentation to T cells.
Conclusions: Our data demonstrate that RSV can induce prolonged upregulation of antigen presentation by LECs, with the potential to facilitate local T cell responses to microbial antigens and allergens and to enhance immunity or in susceptible hosts respiratory allergy.
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