Cell atlas of the Atlantic salmon spleen reveals immune cell heterogeneity and cell-specific responses to bacterial infection
Cell atlas of the Atlantic salmon spleen reveals immune cell heterogeneity and cell-specific responses to bacterial infection
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DOI：
10.1016/j.fsi.2024.109358
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发表时间：
2024-01-17
影响因子：
4.7
通讯作者：
Macqueen，Daniel J.
中科院分区：
文献类型：
--
作者：
Sun，Jianxuan;Daniels，Rose Ruiz;Macqueen，Daniel J.
脾脏是一个保守的次级淋巴器官，在早期有颌脊椎动物中与适应性免疫平行出现。最近的研究已经应用单细胞转录组学来揭示几个物种脾脏的细胞组成，对不同的免疫细胞类型和亚群进行编目。在这项研究中，对商业上重要的硬骨鱼大西洋鲑鱼（萨尔莫salarL.）的51，119个脾核转录组进行了全面研究，将对照动物与用细菌病原体杀鲑鱼气单胞菌攻击的动物进行比较。我们鉴定了代表预期的主要细胞类型的细胞核簇，即T细胞、B细胞、天然类造血细胞、粒细胞、单核吞噬细胞、内皮细胞、间充质细胞、红细胞和血小板。我们发现了几种免疫谱系的异质性，为常驻巨噬细胞和黑色素巨噬细胞、浸润性单核细胞、几种候选树突状细胞亚群和处于不同分化阶段的B细胞（包括浆细胞和anigt +亚群）提供了证据。我们提供了12个候选T细胞亚群的证据，包括cd4+辅助性和调节性T细胞，1个cd8+亚群，3个γδT亚群，以及cd4和cd8双阴性的群体。在气单胞菌感染的早期阶段，不同免疫细胞类型中差异表达的基因数量差异很大，在巨噬细胞和浸润的单核细胞中观察到的变化最大，其次是静息的成熟B细胞。我们的分析提供的证据表明，随着脾脏中B细胞成熟，以及igt + B细胞、T辅助细胞和cd8+细胞以及单核细胞中ccr 9基因的上调，局部炎症反应与肠道免疫细胞群的募集一致，以应对气单胞菌感染。总的来说，这项研究提供了一个新的细胞分辨的角度来看，大西洋鲑鱼脾脏的免疫作用，突出了广泛的异质性隐藏在批量转录组学。我们还提供了大量的细胞特异性标记基因，可用于进一步探索鲑鱼免疫系统的功能和结构组织。
The spleen is a conserved secondary lymphoid organ that emerged in parallel to adaptive immunity in early jawed vertebrates. Recent studies have applied single cell transcriptomics to reveal the cellular composition of spleen in several species, cataloguing diverse immune cell types and subpopulations. In this study, 51,119 spleen nuclei transcriptomes were comprehensively investigated in the commercially important teleost Atlantic salmon (Salmo salarL.), contrasting control animals with those challenged with the bacterial pathogenAeromonas salmonicida. We identified clusters of nuclei representing the expected major cell types, namely T cells, B cells, natural killer-like cells, granulocytes, mononuclear phagocytes, endothelial cells, mesenchymal cells, erythrocytes and thrombocytes. We discovered heterogeneity within several immune lineages, providing evidence for resident macrophages and melanomacrophages, infiltrating monocytes, several candidate dendritic cell subpopulations, and B cells at distinct stages of differentiation, including plasma cells and anigt +subset. We provide evidence for twelve candidate T cell subsets, includingcd4+ T helper and regulatory T cells, onecd8+ subset, three γδT subsets, and populations double negative forcd4andcd8.The number of genes showing differential expression during the early stages ofAeromonasinfection was highly variable across immune cell types, with the largest changes observed in macrophages and infiltrating monocytes, followed by resting mature B cells. Our analysis provides evidence for a local inflammatory response to infection alongside B cell maturation in the spleen, and upregulation ofccr9genes inigt+ B cells, T helper andcd8+ cells, and monocytes, consistent with the recruitment of immune cell populations to the gut to deal withAeromonasinfection. Overall, this study provides a new cell-resolved perspective of the immune actions of Atlantic salmon spleen, highlighting extensive heterogeneity hidden to bulk transcriptomics. We further provide a large catalogue of cell-specific marker genes that can be leveraged to further explore the function and structural organization of the salmonid immune system.