Varpu Rinne, Kirsi Gröndahl-Yli-Hannuksela, Ruth Fair-Mäkelä, Marko Salmi, Pia Rantakari, Tapio Lönnberg, Jukka Alinikula, Annukka Pietikäinen, Jukka Hytönen
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引用次数: 0
摘要
莱姆包虫病是一种由常染色体包柔氏包虫引起的疾病。众所周知,包柔氏菌会诱发长时间的滤泡外免疫反应和异常生殖中心的形成。这种感染无法产生中和类型的免疫,最终形成持续感染。在这里,我们进行了单细胞 RNA 测序,以描述小鼠模型在早期感染包柔氏包虫病期间淋巴结淋巴细胞的免疫状况。我们的研究结果表明,鲍瑞氏菌感染四天后,淋巴结外免疫反应的关键特征包括显著的B细胞增殖、免疫球蛋白类别向IgG3和IgG2b同型转换、浆细胞分化以及通过免疫组化鉴定的淋巴结外B细胞的存在。此外,我们还发现感染导致细胞因子信号抑制基因 Socs1 和 Socs3 上调,以及 B 细胞中与 MHC II 抗原递呈相关的基因下调。我们的研究结果证明了 B 细胞在包柔氏菌感染的免疫反应中的核心作用,并提供了包柔氏菌感染期间决定滤泡外反应和生殖中心反应的机制线索。
Single-cell transcriptome analysis of the early immune response in the lymph nodes of Borrelia burgdorferi-infected mice.
Lyme borreliosis is a disease caused by Borrelia burgdorferi sensu lato bacteria. Borrelia burgdorferi is known to induce prolonged extrafollicular immune responses and abnormal germinal centre formation. The infection fails to generate a neutralizing type of immunity, eventually establishing a persistent infection. Here, we performed single-cell RNA sequencing to characterize the immune landscape of lymph node lymphocytes during the early Borrelia burgdorferi infection in a murine model. Our results indicate key features of an extrafollicular immune response four days after Borrelia burgdorferi infection, including notable B cell proliferation, immunoglobulin class switching to IgG3 and IgG2b isotypes, plasmablast differentiation, and the presence of extrafollicular B cells identified through immunohistochemistry. Additionally, we found infection-derived upregulation of suppressor of cytokine signalling genes Socs1 and Socs3, along with downregulation of genes associated with MHC II antigen presentation in B cells. Our results support the central role of B cells in the immune response of a Borrelia burgdorferi infection, and provide cues of mechanisms behind the determination between extrafollicular and germinal centre responses during Borrelia burgdorferi infection.
期刊介绍:
Microbes and Infection publishes 10 peer-reviewed issues per year in all fields of infection and immunity, covering the different levels of host-microbe interactions, and in particular:
the molecular biology and cell biology of the crosstalk between hosts (human and model organisms) and microbes (viruses, bacteria, parasites and fungi), including molecular virulence and evasion mechanisms.
the immune response to infection, including pathogenesis and host susceptibility.
emerging human infectious diseases.
systems immunology.
molecular epidemiology/genetics of host pathogen interactions.
microbiota and host "interactions".
vaccine development, including novel strategies and adjuvants.
Clinical studies, accounts of clinical trials and biomarker studies in infectious diseases are within the scope of the journal.
Microbes and Infection publishes articles on human pathogens or pathogens of model systems. However, articles on other microbes can be published if they contribute to our understanding of basic mechanisms of host-pathogen interactions. Purely descriptive and preliminary studies are discouraged.