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Monocytes undergo multi-step differentiation in mice during oral infection by Toxoplasma gondii.
Communications Biology ( IF 5.2 ) Pub Date : 2019-12-18 , DOI: 10.1038/s42003-019-0718-6
Aurélie Detavernier 1 , Abdulkader Azouz 1 , Hussein Shehade 1 , Marion Splittgerber 1 , Laurye Van Maele 1 , Muriel Nguyen 1 , Séverine Thomas 1 , Younes Achouri 2 , David Svec 3 , Emilie Calonne 4 , François Fuks 4 , Guillaume Oldenhove 5 , Stanislas Goriely 1
Affiliation  

Monocytes play a major role in the defense against pathogens. They are rapidly mobilized to inflamed sites where they exert both proinflammatory and regulatory effector functions. It is still poorly understood how this dynamic and exceptionally plastic system is controlled at the molecular level. Herein, we evaluated the differentiation process that occurs in Ly6Chi monocytes during oral infection by Toxoplasma gondii. Flow cytometry and single-cell analysis revealed distinct activation status and gene expression profiles in the bone marrow, the spleen and the lamina propria of infected mice. We provide further evidence that acquisition of effector functions, such as the capacity to produce interleukin-27, is accompanied by distinct waves of epigenetic programming, highlighting a role for STAT1/IRF1 in the bone marrow and AP-1/NF-κB in the periphery. This work broadens our understanding of the molecular events that occur in vivo during monocyte differentiation in response to inflammatory cues.

中文翻译:


小鼠在弓形虫口腔感染期间,单核细胞经历多步分化。



单核细胞在防御病原体方面发挥着重要作用。它们迅速动员到发炎部位,发挥促炎和调节效应功能。人们对于如何在分子水平上控制这种动态且异常可塑的系统仍然知之甚少。在此,我们评估了弓形虫口腔感染期间 Ly6Chi 单核细胞中发生的分化过程。流式细胞术和单细胞分析揭示了感染小鼠的骨髓、脾脏和固有层中不同的激活状态和基因表达谱。我们提供了进一步的证据,表明效应功能的获得,例如产生白介素 27 的能力,伴随着不同的表观遗传编程波,强调了 STAT1/IRF1 在骨髓中的作用以及 AP-1/NF-κB 在骨髓中的作用。周边。这项工作拓宽了我们对单核细胞分化过程中响应炎症信号的体内分子事件的理解。
更新日期:2019-12-19
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