Acute effects of TLR3 agonist Poly(I:C) on bone marrow hematopoietic progenitor cells in mice

IF 3.3 4区医学 Q3 IMMUNOLOGY

Immunology letters Pub Date : 2024-09-10 DOI:10.1016/j.imlet.2024.106927

Xin Shu , Yuxuan Xie , Manling Shu , Xiangying Ou , Juan Yang , Zhenyu Wu , Xuan Zhang , Jinfu Zhang , Huihong Zeng , Lijian Shao

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引用次数: 0

Abstract

Hematopoietic progenitor cells (HPCs) in bone marrow with limited abilities for self-renewal and differentiation continuously supply hematopoietic cells through life. When suffering infection or inflammation, HPCs will actively proliferate to provide differentiated hematopoietic cells to maintain hematopoietic homeostasis. Poly(I:C), an agonist of TLR3, can specifically activate Type I interferon (IFN-I) signaling which exerts anti-inflammatory effects and influence hematopoiesis after infection. However, the effects of Poly(I:C)-induced IFN-I on the bone marrow hematopoietic system still deserve attention. In this study, our results revealed the efficacy of the IFN-I model, with a remarkably decrease in HPCs and a sharp elevation in LSKs numbers after single dose of Poly(I:C) injection. Apoptotic ratios of HPCs and LSKs significantly increased 48 h after Poly(I:C) treatment. Application of Poly(I:C) prompted the transition of HPCs and LSKs from G0 to G1 phases, potentially leading to the accelerated exhaustion of HPCs. From the cobblestone area-forming cell (CAFC) assay, we speculate that Poly(I:C) impairs the differentiation capacity of HPCs as well as their colony-forming ability. RT-qPCR and immunohistochemistry revealed significant upregulation of IFN-I associated genes and proteins following Poly(I:C) treatment. In conclusion, a single dose of Poly(I:C) induced an acute detrimental effect on HPCs within 48 h potentially due to TLR3 engagement. This activation cascaded into a robust IFN-I response emanating from the bone marrow, underscoring the intricate immunological dynamics at play following Poly(I:C) intervention.

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TLR3 激动剂 Poly(I:C) 对小鼠骨髓造血祖细胞的急性影响

骨髓中的造血祖细胞（HPCs）具有有限的自我更新和分化能力，可持续提供造血细胞。当受到感染或出现炎症时，造血祖细胞会积极增殖，提供分化的造血细胞，以维持造血平衡。TLR3的激动剂Poly(I:C)能特异性激活I型干扰素（IFN-I）信号，从而发挥抗炎作用，影响感染后的造血功能。然而，Poly(I:C)诱导的 IFN-I 对骨髓造血系统的影响仍值得关注。在本研究中，我们的结果显示了 IFN-I 模型的有效性，单剂量注射 Poly(I:C) 后，HPCs 显著减少，LSKs 数量急剧增加。Poly(I:C)治疗48小时后，HPCs和LSKs的凋亡率明显增加。应用Poly(I:C)促使HPCs和LSKs从G0期过渡到G1期，可能导致HPCs加速衰竭。通过鹅卵石面积形成细胞（CAFC）试验，我们推测 Poly(I:C) 会损害 HPCs 的分化能力及其集落形成能力。RT-qPCR 和免疫组化显示，Poly(I:C) 处理后，IFN-I 相关基因和蛋白显著上调。总之，单剂量的 Poly(I:C) 可在 48 小时内对 HPCs 产生急性有害影响，这可能是 TLR3 参与所致。这种激活会导致骨髓产生强烈的 IFN-I 反应，从而突显出聚(I:C)干预后错综复杂的免疫动态。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunology letters 医学-免疫学

CiteScore

7.60

自引率

0.00%

发文量

审稿时长

44 days

期刊介绍： Immunology Letters provides a vehicle for the speedy publication of experimental papers, (mini)Reviews and Letters to the Editor addressing all aspects of molecular and cellular immunology. The essential criteria for publication will be clarity, experimental soundness and novelty. Results contradictory to current accepted thinking or ideas divergent from actual dogmas will be considered for publication provided that they are based on solid experimental findings. Preference will be given to papers of immediate importance to other investigators, either by their experimental data, new ideas or new methodology. Scientific correspondence to the Editor-in-Chief related to the published papers may also be accepted provided that they are short and scientifically relevant to the papers mentioned, in order to provide a continuing forum for discussion.