Identification of a Unique Hybrid Macrophage-Polarization State following Recovery from Lipopolysaccharide Tolerance
Identification of a Unique Hybrid Macrophage-Polarization State following Recovery from Lipopolysaccharide Tolerance
复制标题
DOI：
10.4049/jimmunol.1301722
复制
发表时间：
2014-01-01
影响因子：
4.4
通讯作者：
Carmody, Ruaidhri J.
中科院分区：
文献类型：
--
作者：
O'Carroll, Christine;Fagan, Ailis;Carmody, Ruaidhri J.
LPS耐受是对反复暴露于LPS的必要免疫稳态应答，其防止过度炎症应答。LPS耐受性诱导巨噬细胞中改变的反应性状态，导致促炎基因表达的抑制和介导炎症消退的因子的表达增加。在这项研究中，我们分析了转录可塑性的巨噬细胞LPS耐受性使用全基因组转录谱。我们证明，LPS耐受是一种短暂的状态，促炎基因的表达恢复到与LPS急性反应相当的水平。然而，在从LPS耐受性恢复后，许多基因保持锁定在可耐受状态，包括IL-33、CD 86、IL-10和NFIL 3。此外，我们确定了一些基因独特的诱导后恢复LPS耐受。因此，巨噬细胞在从LPS耐受性恢复后采用独特的转录谱，并且具有Ag呈递、抗病毒应答和转录因子的调节剂的不同表达模式。我们的数据表明，从LPS耐受性恢复导致混合巨噬细胞活化状态，其本质上是促炎性和杀微生物的，但具有与LPS耐受性和LPS活化的巨噬细胞不同的调节性抗炎特征。
LPS tolerance is an essential immune-homeostatic response to repeated exposure to LPS that prevents excessive inflammatory responses. LPS tolerance induces a state of altered responsiveness in macrophages, resulting in repression of proinflammatory gene expression and increased expression of factors that mediate the resolution of inflammation. In this study, we analyzed the transcriptional plasticity of macrophages following LPS tolerance using genome-wide transcriptional profiling. We demonstrate that LPS tolerance is a transient state and that the expression of proinflammatory genes is restored to levels comparable to the acute response to LPS. However, following recovery from LPS tolerance a number of genes remained locked in a tolerizable state, including IL-33, CD86, IL-10, and NFIL3. Furthermore, we identified of a number of genes uniquely induced following recovery from LPS tolerance. Thus, macrophages adopt a unique transcriptional profile following recovery from LPS tolerance and have a distinct expression pattern of regulators of Ag presentation, antiviral responses, and transcription factors. Our data suggest that recovery from LPS tolerance leads to a hybrid macrophage activation state that is proinflammatory and microbicidal in nature but that possesses a regulatory anti-inflammatory profile distinct from that of LPS-tolerant and LPS-activated macrophages.