PDF(Pubmed)
Abstract：
BACKGROUND: Mycobacteria bloodstream infections are common in immunocompromised people and usually have disastrous consequences. As the primary phagocytes in the bloodstream, monocytes and neutrophils play critical roles in the fight against bloodstream mycobacteria infections. In contrast to macrophages, the responses of monocytes infected with the mycobacteria have been less investigated.
RESULTS: In this study, we first established a protocol for infection of non-adherent monocyte-like THP-1 cells (i.e. without the differentiation induced by phorbol 12-myristate 13-acetate (PMA) by bacillus Calmette-Guérin (BCG). Via the protocol, we were then capable of exploring the global transcriptomic profiles of non-adherent THP-1 cells infected with BCG, and found that NF-κB, MAPK and PI3K-Akt signaling pathways were enhanced, as well as some inflammatory chemokine/cytokine genes (e.g. CCL4, CXCL10, TNF and IL-1β) were up-regulated. Surprisingly, the Akt-HIF-mTOR signaling pathway was also activated, which induces trained immunity. In this in vitro infection model, increased cytokine responses to lipopolysaccharides (LPS) restimulation, higher cell viability, and decreased Candida albicans loads were observed.
CONCLUSIONS: We have first characterized the transcriptomic profiles of BCG-infected non-adherent THP-1 cells, and first developed a trained immunity in vitro model of the cells.
RESULTS: In this study, we first established a protocol for infection of non-adherent monocyte-like THP-1 cells (i.e. without the differentiation induced by phorbol 12-myristate 13-acetate (PMA) by bacillus Calmette-Guérin (BCG). Via the protocol, we were then capable of exploring the global transcriptomic profiles of non-adherent THP-1 cells infected with BCG, and found that NF-κB, MAPK and PI3K-Akt signaling pathways were enhanced, as well as some inflammatory chemokine/cytokine genes (e.g. CCL4, CXCL10, TNF and IL-1β) were up-regulated. Surprisingly, the Akt-HIF-mTOR signaling pathway was also activated, which induces trained immunity. In this in vitro infection model, increased cytokine responses to lipopolysaccharides (LPS) restimulation, higher cell viability, and decreased Candida albicans loads were observed.
CONCLUSIONS: We have first characterized the transcriptomic profiles of BCG-infected non-adherent THP-1 cells, and first developed a trained immunity in vitro model of the cells.
摘要：
背景：分枝杆菌血流感染在免疫功能低下的人群中很常见，通常会带来灾难性的后果。作为血液中的初级吞噬细胞，单核细胞和中性粒细胞在对抗血流分枝杆菌感染中发挥关键作用。与巨噬细胞相反，感染分枝杆菌的单核细胞的反应研究较少。
结果：在这项研究中，我们首先建立了感染非贴壁单核细胞样THP-1细胞的方案(即没有卡介苗(BCG)诱导的佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)分化.通过协议，然后，我们能够探索被BCG感染的非贴壁THP-1细胞的整体转录组学谱，发现NF-κB,MAPK和PI3K-Akt信号通路增强,以及一些炎性趋化因子/细胞因子基因(例如CCL4、CXCL10、TNF和IL-1β)被上调。令人惊讶的是,Akt-HIF-mTOR信号通路也被激活，诱导训练有素的免疫力。在这个体外感染模型中,对脂多糖（LPS）再刺激的细胞因子反应增加，更高的细胞活力，观察到白色念珠菌负荷降低。
结论：我们首先表征了BCG感染的非贴壁THP-1细胞的转录组特征，并首先开发了一种训练有素的细胞体外免疫模型。
结果：在这项研究中，我们首先建立了感染非贴壁单核细胞样THP-1细胞的方案(即没有卡介苗(BCG)诱导的佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)分化.通过协议，然后，我们能够探索被BCG感染的非贴壁THP-1细胞的整体转录组学谱，发现NF-κB,MAPK和PI3K-Akt信号通路增强,以及一些炎性趋化因子/细胞因子基因(例如CCL4、CXCL10、TNF和IL-1β)被上调。令人惊讶的是,Akt-HIF-mTOR信号通路也被激活，诱导训练有素的免疫力。在这个体外感染模型中,对脂多糖（LPS）再刺激的细胞因子反应增加，更高的细胞活力，观察到白色念珠菌负荷降低。
结论：我们首先表征了BCG感染的非贴壁THP-1细胞的转录组特征，并首先开发了一种训练有素的细胞体外免疫模型。
