Regulation of dendritic cells and their progenitors in infectious diseases

传染病中树突状细胞及其祖细胞的调节

• 批准号: 219943157
• 负责人: Privatdozentin Dr. Stella E. Autenrieth, Ph.D.
• 金额: --
• 依托单位: Abteilung Stammzellen und Krebs
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/219943157?language=en
• 关键词: Regulation; dendritic; cells; their; progenitors

Upon the fight against invading pathogens mechanisms and events such as mobilization to the sites of infection or apoptosis lead to the consumption of immune cells. Dendritic cells (DCs) are key players of the adaptive immune response and important components in immunity against infections. Therefore, the regulation of DCs and their progenitors upon infection/inflammation is an emerging field of interest. Using the model pathogen Yersinia enterocolitica (Ye) in an experimental mouse infection model we found that Ye infection causes a pronounced reduction of the number of splenic DCs. This effect was dependent on TLR4 and TRIF signaling, and the net result of Ye-induced faster DC turnover and sup-pression of de novo DC generation. However, the mechanism underlying this remains elusive. We hypothesize that Ye may affect hematopoietic stem and progenitor cells (HSPCs) and DC precur-sors by microbial and/or inflammatory signals, such as TLR ligands, pathogenicity factors and interferons and that this might influence immunity against the pathogen. Therefore, the regulation of HSPCs and their progeny with focus on DC progenitors will be analyzed upon infection with different bacterial pathogens to elucidate possible general regulation mechanisms. Specifically we will focus on analyzing the basic influence of microbial (TLR signaling, direct and indirect effects) and inflammatory (interferons, chemokines and growth factors) signals on survival/proliferation, migration and differentiation of HSPCs and DC precursors. Knowledge about this will not only give new insights into basic DC biology, but may also identify new therapeutic targets/diagnostic markers in infectious diseases.

在对抗入侵病原体的过程中，感染部位的动员或细胞凋亡等机制和事件会导致免疫细胞的消耗。树突状细胞(DC)是获得性免疫反应的关键分子，也是抗感染免疫的重要组成部分。因此，DC及其前体细胞对感染/炎症的调控是一个新兴的研究领域。利用模型病原体小肠结肠炎耶尔森氏菌(Ye)在实验性小鼠感染模型中发现，Ye感染导致脾DC数量显着减少。这一效应依赖于TLR4和TRIF信号通路，是Ye诱导的DC更新加快和抑制新生DC生成的综合结果。然而，这背后的机制仍然难以捉摸。我们推测YE可能通过微生物和/或炎症信号，如TLR配体、致病因子和干扰素影响造血干/祖细胞和DC前体，从而影响对病原体的免疫。因此，我们将分析HSPC及其后代在感染不同细菌病原体时对DC祖细胞的调控，以阐明可能的一般调控机制。具体而言，我们将重点分析微生物信号(TLR信号，直接和间接效应)和炎症信号(干扰素、趋化因子和生长因子)对HSPC和DC前体细胞存活/增殖、迁移和分化的基本影响。对此的了解不仅将为DC的基本生物学提供新的见解，而且还可能确定传染病的新治疗靶点/诊断标记物。

项目成果

Innate immune system favors emergency monopoiesis at the expense of DC‐differentiation to control systemic bacterial infection in mice

先天免疫系统有利于紧急垄断，但以牺牲 DC-分化为代价来控制小鼠的全身细菌感染

• DOI: 10.1002/eji.201545530
• 发表时间: 2015
• 期刊: European Journal of Immunology
• 影响因子: 5.4
• 作者: Pasquevich KA;Bieber K;Günter M;Grauer M;Pötz O;Schleicher U;Biedermann T;Beer-Hammer S;Bühring HJ;Rammensee HG;Zender L;Autenrieth IB;Lengerke C;Autenrieth SE
• 通讯作者: Autenrieth SE