Ye Yutao, Liu Jun, Guo Yang, Gao Yujie, Rao Jiayue, Su Rigu, Zhang Lu, Huang Zikun, Luo Qing, Li Junming
Jiangxi Province Key Laboratory of Laboratory Medicine, Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Front Microbiol. 2022 Mar 31;13:829870. doi: 10.3389/fmicb.2022.829870. eCollection 2022.
Foamy macrophages are present during the course of () infection and seems to be nutrient-rich reservoir and secure reservoir for the bacilli, which leads to bacterial persistence and infection transmission. Peroxisome proliferator activated receptor γ (PPARγ) is a key transcription factor for cholesterol metabolism in macrophages and its role in regulating atherosclerosis related foamy macrophages (FMs) formation has been well-studied. However, knowledge about the mechanism of PPARγ regulating infection induced FM formation remains very limited. In this study, we investigate the functional role of PPARγ in H37Ra infection-induced foamy macrophages formation. H37Ra infection induced a time-dependent decreased expression of PPARγ that paralleled the augmented lipid body formation in THP1-derived macrophages. PPARγ antagonist GW9662 significantly potentiate H37Ra induced lipid body formation and inhibit ABCG1 expression, overexpression of ABCG1 by transduced macrophages with lentivirus significantly reversed the promotion effect of GW9662 on FM formation. Moreover, Treatment with a TLR2 neutralizing antibody ameliorated the activation of ABCG1 by H37Ra without significantly effecting the suppression of PPARγ, suggesting a greater role for TLR2 to regulate ABCG1 compared to PPARγ. Overall, this study showed that PPARγ is involved in ameliorating FM formation by regulating ABCG1 expression, these observations expose a novel role of PPARγ in the infection induced FM formation.
泡沫状巨噬细胞在（）感染过程中存在，似乎是细菌的营养丰富储存库和安全储存库，这导致细菌持续存在和感染传播。过氧化物酶体增殖物激活受体γ（PPARγ）是巨噬细胞中胆固醇代谢的关键转录因子，其在调节动脉粥样硬化相关泡沫状巨噬细胞（FMs）形成中的作用已得到充分研究。然而，关于PPARγ调节感染诱导的FMs形成机制的知识仍然非常有限。在本研究中，我们研究了PPARγ在H37Ra感染诱导的泡沫状巨噬细胞形成中的功能作用。H37Ra感染诱导PPARγ表达呈时间依赖性下降，这与THP1衍生巨噬细胞中脂质体形成增加平行。PPARγ拮抗剂GW9662显著增强H37Ra诱导的脂质体形成并抑制ABCG1表达，用慢病毒转导巨噬细胞过表达ABCG1可显著逆转GW9662对FMs形成的促进作用。此外，用TLR2中和抗体处理可改善H37Ra对ABCG1的激活，而对PPARγ的抑制没有显著影响，这表明与PPARγ相比，TLR2在调节ABCG1方面发挥更大作用。总体而言，本研究表明PPARγ通过调节ABCG1表达参与改善FMs形成，这些观察结果揭示了PPARγ在感染诱导的FMs形成中的新作用。
