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犬瘟热病毒感染后犬肺部免疫反应的表型和转录变化。

Phenotypic and Transcriptional Changes of Pulmonary Immune Responses in Dogs Following Canine Distemper Virus Infection.

机构信息

Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.

Center for Systems Neuroscience (ZSN), 30559 Hannover, Germany.

出版信息

Int J Mol Sci. 2022 Sep 2;23(17):10019. doi: 10.3390/ijms231710019.

DOI:10.3390/ijms231710019
PMID:36077417
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9456005/
Abstract

Canine distemper virus (CDV), a morbillivirus within the family , is a highly contagious infectious agent causing a multisystemic, devastating disease in a broad range of host species, characterized by severe immunosuppression, encephalitis and pneumonia. The present study aimed at investigating pulmonary immune responses of CDV-infected dogs in situ using immunohistochemistry and whole transcriptome analyses by bulk RNA sequencing. Spatiotemporal analysis of phenotypic changes revealed pulmonary immune responses primarily driven by MHC-II, Iba-1 and CD204 innate immune cells during acute and subacute infection phases, which paralleled pathologic lesion development and coincided with high viral loads in CDV-infected lungs. CD20 B cell numbers initially declined, followed by lymphoid repopulation in the advanced disease phase. Transcriptome analysis demonstrated an increased expression of transcripts related to innate immunity, antiviral defense mechanisms, type I interferon responses and regulation of cell death in the lung of CDV-infected dogs. Molecular analyses also revealed disturbed cytokine responses with a pro-inflammatory M1 macrophage polarization and impaired mucociliary defense in CDV-infected lungs. The exploratory study provides detailed data on CDV-related pulmonary immune responses, expanding the list of immunologic parameters potentially leading to viral elimination and virus-induced pulmonary immunopathology in canine distemper.

摘要

犬瘟热病毒（CDV）是副黏病毒科的一种麻疹病毒，是一种高传染性的病原体，可引起广泛宿主物种的多系统、破坏性疾病，其特征是严重的免疫抑制、脑炎和肺炎。本研究旨在使用免疫组织化学和批量 RNA 测序的全转录组分析原位研究 CDV 感染犬的肺部免疫反应。表型变化的时空分析表明，在急性和亚急性感染阶段，主要由 MHC-II、Iba-1 和 CD204 先天免疫细胞驱动肺部免疫反应，与病理损伤的发展平行，并与 CDV 感染肺中的高病毒载量一致。CD20 B 细胞数量最初下降，随后在疾病晚期出现淋巴样再殖。转录组分析表明，CDV 感染犬肺部的先天免疫、抗病毒防御机制、I 型干扰素反应和细胞死亡调节相关的转录本表达增加。分子分析还表明，CDV 感染的肺部存在细胞因子反应紊乱，M1 巨噬细胞极化呈促炎状态，黏膜纤毛防御受损。这项探索性研究提供了与 CDV 相关的肺部免疫反应的详细数据，扩大了潜在导致病毒清除和病毒引起的犬瘟热肺免疫病理学的免疫参数列表。

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