Homing of Antigen-Presenting Cells in Head Kidney and Spleen - Salmon Head Kidney Hosts Diverse APC Types.
Homing of Antigen-Presenting Cells in Head Kidney and Spleen - Salmon Head Kidney Hosts Diverse APC Types.
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DOI：
10.3389/fimmu.2013.00137
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发表时间：
2013
影响因子：
7.3
通讯作者：
Jørgensen JB
中科院分区：
文献类型：
--
作者：
Iliev DB;Thim H;Lagos L;Olsen R;Jørgensen JB
淋巴结和脾是哺乳动物抗原提呈细胞(APC)启动和协调抗原特异性免疫反应的主要器官。与哺乳动物不同，硬骨鱼没有淋巴结，一个有趣的问题是，替代器官是否可以作为硬骨鱼抗原呈递的场所。在本研究中，在2 周内，在大量的鲑鱼头肾(HK)MHCII+细胞中检测到荧光卵清蛋白(OVA)和CpG寡核苷酸(ODN)，而在脾中检测到的比例是短暂的，从注射后第1天开始下降。体外研究进一步揭示了在香港发现的不同MHCII+细胞类型的特性。具有高吞噬和处理卵子能力的MHCII+细胞亚群的超微结构表明，这些细胞能够进行结构性巨噬细胞吞噬。在CpG ODN刺激下，这些细胞上调CD86，并产生非常高水平的肿瘤坏死因子mRNA，表明这些细胞是专业的APC，与巨噬细胞和树突状细胞(DC)相关。一群HK粒细胞高水平表达表面MHCII，并在CpG刺激下上调大部分被测试的APC标记基因。虽然这些粒细胞表达肿瘤坏死因子的能力较弱，但它们具有相对较高的IL-1β基础水平，并且与其他类型的HK细胞相比，CpG刺激上调了IL-1β及其信号和诱骗受体，达到最高水平。有趣的是，IL-1LC3mRNA在粒细胞中的高表达与高自噬通量相关，如β-II转换所证明的那样。最近发现自噬与IL-1β的加工和分泌有关，目前的数据表明，鲑鱼的颗粒细胞，也许还有其他硬骨鱼物种的颗粒细胞，可能是研究自噬参与调节脊椎动物免疫反应的一个有价值的模型。
Lymph nodes and spleen are major organs where mammalian antigen-presenting cells (APCs) initiate and orchestrate Ag-specific immune responses. Unlike mammals, teleosts lack lymph nodes and an interesting question is whether alternative organs may serve as sites for antigen presentation in teleosts. In the current study, fluorescent ovalbumin (Ova) and CpG oligonucleotides (ODNs) injected intra-abdominally were detected in significant numbers of salmon head kidney (HK) MHCII+ cells over a period of 2 weeks while in spleen the percentage of these was transient and declined from day 1 post injection. In vitro studies further shed light on the properties of the diverse MHCII+ cell types found in HK. The ultrastructure of a subpopulation of MHCII+ cells with a high capacity to endocytose and process Ova indicated that these were able to perform constitutive macropinocytosis. Upon stimulation with CpG ODNs these cells upregulated CD86 and gave very high levels of TNF mRNA indicating that these are professional APCs, related to macrophages and dendritic cells (DCs). A subpopulation of HK granulocytes expressed high levels of surface MHCII and upon CpG stimulation upregulated most of the tested APC marker genes. Although these granulocytes expressed TNF weakly, they had relatively high basal levels of IL-1β mRNA and the CpG stimulation upregulated IL-1β, along with its signaling and decoy receptors, to the highest levels as compared to other HK cell types. Interestingly, the high expression of IL-1β mRNA in the granulocytes correlated with a high autophagy flux as demonstrated by LC3-II conversion. Autophagy has recently been found to be implicated in IL-1β processing and secretion and the presented data suggests that granulocytes of salmon, and perhaps other teleost species, may serve as a valuable model to study the involvement of autophagy in regulation of the vertebrate immune response.