Macrophages, rather than DCs, are responsible for inflammasome activity in the GM-CSF BMDC model
Macrophages, rather than DCs, are responsible for inflammasome activity in the GM-CSF BMDC model
复制标题
DOI：
10.1038/s41590-019-0313-5
复制
发表时间：
2019-04-01
影响因子：
30.5
通讯作者：
Gerlic, Motti
中科院分区：
文献类型：
--
作者：
Erlich, Ziv;Shlomovitz, Inbar;Gerlic, Motti
炎性小体是针对微生物感染的先天免疫防御的最重要机制之一，但也已知通过加工和释放细胞因子IL-1 β来驱动各种炎性疾病。随着对炎性小体在疾病中的调节和作用的研究迅速扩大，已经提出包括树突状细胞（DC）在内的多种细胞类型是炎性小体感受态的。在这里，我们描述了一个主要的故障，在广泛使用的DC-炎性模型的骨髓来源的树突状细胞（BMDCs）产生的细胞因子粒细胞-巨噬细胞集落刺激因子（GM-CSF）。我们发现，在GM-CSF骨髓来源的细胞群中，单核细胞来源的巨噬细胞，而不是BMDC，负责炎性小体激活和IL-1 β分泌。因此，GM-CSF骨髓来源的细胞不应用于得出DC依赖性炎性小体生物学的结论，尽管它们仍然是分析单核细胞-巨噬细胞中炎性小体反应的有用工具。
Inflammasomes are one of the most important mechanisms for innate immune defense against microbial infection but are also known to drive various inflammatory disorders via processing and release of the cytokine IL-1 beta. As research into the regulation and effects of inflammasomes in disease has rapidly expanded, a variety of cell types, including dendritic cells (DCs), have been suggested to be inflammasome competent. Here we describe a major fault in the widely used DC-inflammasome model of bone marrow-derived dendritic cells (BMDCs) generated with the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). We found that among GM-CSF bone marrow-derived cell populations, monocyte-derived macrophages, rather than BMDCs, were responsible for inflammasome activation and IL-1 beta secretion. Therefore, GM-CSF bone marrow-derived cells should not be used to draw conclusions about DC-dependent inflammasome biology, although they remain a useful tool for analysis of inflammasome responses in monocytes-macrophages.