Computational Biology Group, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4362, Esch-sur-Alzette, Luxembourg.
Inflammation and Macrophage Plasticity laboratory, CIC bioGUNE-BRTA (Basque Research and Technology Alliance), Derio, 48160, Spain.
Cell Death Dis. 2021 Aug 17;12(9):798. doi: 10.1038/s41419-021-04075-y.
Immunomodulation strategies are crucial for several biomedical applications. However, the immune system is highly heterogeneous and its functional responses to infections remains elusive. Indeed, the characterization of immune response particularities to different pathogens is needed to identify immunomodulatory candidates. To address this issue, we compiled a comprehensive map of functional immune cell states of mouse in response to 12 pathogens. To create this atlas, we developed a single-cell-based computational method that partitions heterogeneous cell types into functionally distinct states and simultaneously identifies modules of functionally relevant genes characterizing them. We identified 295 functional states using 114 datasets of six immune cell types, creating a Catalogus Immune Muris. As a result, we found common as well as pathogen-specific functional states and experimentally characterized the function of an unknown macrophage cell state that modulates the response to Salmonella Typhimurium infection. Thus, we expect our Catalogus Immune Muris to be an important resource for studies aiming at discovering new immunomodulatory candidates.
免疫调节策略对于许多生物医学应用至关重要。然而,免疫系统高度异质,其对感染的功能反应仍然难以捉摸。事实上,需要对不同病原体的免疫反应特殊性进行特征描述,以确定免疫调节候选物。为了解决这个问题,我们编制了一张综合图谱,描述了小鼠对 12 种病原体的功能性免疫细胞状态。为了创建这个图谱,我们开发了一种基于单细胞的计算方法,将异质细胞类型划分为功能不同的状态,并同时识别出功能相关基因模块来对其进行特征描述。我们使用六种免疫细胞类型的 114 个数据集来识别 295 个功能状态,创建了一个 Catalogus Immune Muris。结果,我们发现了共同的和特定于病原体的功能状态,并对一种调节沙门氏菌感染反应的未知巨噬细胞状态的功能进行了实验表征。因此,我们预计我们的 Catalogus Immune Muris 将成为发现新的免疫调节候选物的研究的重要资源。