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猪树突状细胞亚群和固有免疫反应的高分辨率分析

High-Resolution Profiling of Innate Immune Responses by Porcine Dendritic Cell Subsets and .

机构信息

Institute of Virology and Immunology, Mittelhäusern, Switzerland.

Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland.

出版信息

Front Immunol. 2020 Jul 7;11:1429. doi: 10.3389/fimmu.2020.01429. eCollection 2020.

DOI:10.3389/fimmu.2020.01429
PMID:32733474
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7358342/
Abstract

The present study investigated the transcriptomic response of porcine dendritic cells (DC) to innate stimulation and . The aim was to identify DC subset-specialization, suitable Toll-like receptor (TLR) ligands targeting plasmacytoid DC (pDC), and the DC activation profile during highly and low virulent classical swine fever virus (CSFV, strain Eystrup and Pinar del Rio, respectively) infection, chosen as model for a virus causing a severe immunopathology. After identification of porcine conventional DC (cDC) 1, cDC2, pDC and a monocyte-derived subset in lymphoid tissues, we characterized DC activation using transcriptomics, and focused on chemokines, interferons, cytokines, as well as on co-stimulatory and inhibitory molecules. We demonstrate that porcine pDC provide important signals for Th1 and interferon responses, with CpG triggering the strongest responses in pDC. DC isolated early after infection of pigs with either of the two CSFV strains showed prominent upregulation of , and , as well as of the cytokines . Transcription of and many interferon genes were mostly restricted to pDC. Interestingly, the infection was associated with a prominent induction of inhibitory and cell death receptors. When comparing low and highly virulent CSFV strains, the latter induced a stronger inflammatory and antiviral response but a weaker cell cycle response, and reduced antigen presentation functions of DC. Taken together, we provide high-resolution information on DC activation in pigs, as well as information on how DC modulation could be linked to CSFV immunopathology.

摘要

本研究调查了猪树突状细胞 (DC) 对内源性刺激的转录组反应 和 。目的是确定 DC 亚群特化、适合浆细胞样 DC (pDC) 的 Toll 样受体 (TLR) 配体，以及在高毒力和低毒力经典猪瘟病毒 (CSFV，分别为 Eystrup 和 Pinar del Rio 株) 感染期间的 DC 激活谱，选择该病毒作为引起严重免疫病理学的模型。在鉴定出猪常规 DC (cDC) 1、cDC2、pDC 和单核细胞衍生的淋巴组织亚群后，我们使用转录组学来表征 DC 激活，并重点关注趋化因子、干扰素、细胞因子以及共刺激和抑制分子。我们证明猪 pDC 为 Th1 和干扰素反应提供重要信号，CpG 触发 pDC 最强反应。感染两种 CSFV 株的猪早期分离的 DC 显示出 和 以及细胞因子 的明显上调 。 和许多干扰素基因的转录主要局限于 pDC。有趣的是，感染与抑制性和细胞死亡受体的显著诱导有关。当比较低毒力和高毒力 CSFV 株时，后者诱导更强的炎症和抗病毒反应，但较弱的细胞周期反应，并降低 DC 的抗原呈递功能。总之，我们提供了猪 DC 激活的高分辨率信息，以及 DC 调节如何与 CSFV 免疫病理学相关的信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c24/7358342/c86c6fd43c95/fimmu-11-01429-g0008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c24/7358342/c86c6fd43c95/fimmu-11-01429-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c24/7358342/f56fe627821d/fimmu-11-01429-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c24/7358342/18b0399a9e03/fimmu-11-01429-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c24/7358342/3d95a1702cdc/fimmu-11-01429-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c24/7358342/e6327931c2f1/fimmu-11-01429-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c24/7358342/8274f09c542a/fimmu-11-01429-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c24/7358342/13eb616bc138/fimmu-11-01429-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c24/7358342/e4a01f989284/fimmu-11-01429-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c24/7358342/c86c6fd43c95/fimmu-11-01429-g0008.jpg

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