Cellular and transcriptome signatures unveiled by single-cell RNA-Seq following ex vivo infection of murine splenocytes with Borrelia burgdorferi.
Cellular and transcriptome signatures unveiled by single-cell RNA-Seq following ex vivo infection of murine splenocytes with Borrelia burgdorferi.
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DOI：
10.3389/fimmu.2023.1296580
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
莱姆病是美国最常见的蜱媒传染病，由螺旋体病原体伯氏疏螺旋体（Borrelia burgdorferi，Bb）引起。不同的宿主反应中观察到的敏感和耐药品系的近交系小鼠感染Bb后，反映了一个子集的炎症反应中观察到的人类莱姆病。后基因组方法和基因组数据集的出现使得能够剖析宿主反应以推进用于限制病原体传播和/或莱姆病治疗的治疗选择。在这项研究中，我们使用单细胞RNA-Seq分析结合小鼠基因组学，利用GFP表达Bb对GFP+脾细胞和GFP −旁观者细胞进行分选，以发现有助于针对Bb的免疫反应早期阶段的新分子和细胞特征。这些数据解释了C3 H/HeN小鼠脾中性粒细胞、巨噬细胞、NK细胞、B细胞和T细胞对B B感染应答的异质性。在从GFP+脾细胞聚集的嗜中性粒细胞和巨噬细胞中观察到凋亡相关基因的mRNA丰度增加。此外，补体介导的吞噬相关基因，如C1q和Ficolin升高的炎症巨噬细胞亚群，这表明这些基因的上调，在与BB感染的中性粒细胞的巨噬细胞的相互作用。此外，DUSP1在调节Bb感染的中性粒细胞中Casp3和促炎细胞因子Cxcl1、Cxcl2、Illb和Ccl5的表达中的作用被鉴定。这些发现作为鼠脾细胞中细胞表型/生物标志物的不断增长的目录，可用于限制螺旋体负荷，以限制莱姆病因子通过储库宿主向人类的传播。
Lyme disease, the most common tick-borne infectious disease in the US, is caused by a spirochetal pathogen Borrelia burgdorferi (Bb). Distinct host responses are observed in susceptible and resistant strains of inbred of mice following infection with Bb reflecting a subset of inflammatory responses observed in human Lyme disease. The advent of post-genomic methodologies and genomic data sets enables dissecting the host responses to advance therapeutic options for limiting the pathogen transmission and/or treatment of Lyme disease. In this study, we used single-cell RNA-Seq analysis in conjunction with mouse genomics exploiting GFP-expressing Bb to sort GFP+ splenocytes and GFP− bystander cells to uncover novel molecular and cellular signatures that contribute to early stages of immune responses against Bb. These data decoded the heterogeneity of splenic neutrophils, macrophages, NK cells, B cells, and T cells in C3H/HeN mice in response to Bb infection. Increased mRNA abundance of apoptosis-related genes was observed in neutrophils and macrophages clustered from GFP+ splenocytes. Moreover, complement-mediated phagocytosis-related genes such as C1q and Ficolin were elevated in an inflammatory macrophage subset, suggesting upregulation of these genes during the interaction of macrophages with Bb-infected neutrophils. In addition, the role of DUSP1 in regulating the expression of Casp3 and pro-inflammatory cytokines Cxcl1, Cxcl2, Il1b, and Ccl5 in Bb-infected neutrophils were identified. These findings serve as a growing catalog of cell phenotypes/biomarkers among murine splenocytes that can be exploited for limiting spirochetal burden to limit the transmission of the agent of Lyme disease to humans via reservoir hosts.
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伯氏疏螺旋体碱性膜蛋白A刺激小鼠巨噬细胞分泌特异性趋化因子
影响因子：
3.6
作者：
Peng Y;Liang Z;Liu A;Li E;Dai X;Bai R;Ji Z;Jian M;Ma M;Tao L;Bao F;Wang F;Bi Y;Ding Z;Manzama-Esso A
通讯作者：
Manzama-Esso A
影响因子：
5.4
作者：
Oosting, Marije;van de Veerdonk, Frank L.;Kanneganti, Thirumala-Devi;Sturm, Patrick;Verschueren, Ineke;Berende, Anneleen;van der Meer, Jos W. M.;Kullberg, Bart-Jan;Netea, Mihai G.;Joosten, Leo A. B.
通讯作者：
Joosten, Leo A. B.
影响因子：
4.6
作者：
Robitaille AC;Caron E;Zucchini N;Mukawera E;Adam D;Mariani MK;Gélinas A;Fortin A;Brochiero E;Grandvaux N
通讯作者：
Grandvaux N
主机转录组对Borrelia Burgdorferi Sensu Lato的反应。
影响因子：
3.2
作者：
Thompson D;Watt JA;Brissette CA
通讯作者：
Brissette CA
DOI：
10.4049/jimmunol.1102541
发表时间：
2012-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hemmi H;Zaidi N;Wang B;Matos I;Fiorese C;Lubkin A;Zbytnuik L;Suda K;Zhang K;Noda M;Kaisho T;Steinman RM;Idoyaga J
通讯作者：
Idoyaga J