CD36 neutralisation blunts TLR2-IRF7 but not IRF3 pathway in neonatal mouse brain and immature human microglia following innate immune challenge.
CD36 neutralisation blunts TLR2-IRF7 but not IRF3 pathway in neonatal mouse brain and immature human microglia following innate immune challenge.
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DOI：
10.1038/s41598-023-29423-0
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发表时间：
2023-02-09
影响因子：
4.6
通讯作者：
Kriz, Jasna
中科院分区：
文献类型：
--
作者：
Gadagkar, Shruti Gururaj;Lalancette-Hebert, Melanie;Thammisetty, Sai Sampath;Vexler, Zinaida S.;Kriz, Jasna
新生儿脑中的先天免疫应答与小胶质细胞的强烈激活和Toll样受体（TLR）的诱导相关。迄今为止，清道夫受体CD 36在TLR调节，特别是TLR 2信号传导中的作用已经在成人脑中得到很好的确立。然而，TLR 4、TLR 2和CD 36之间的串扰及其在新生儿脑中的免疫原性影响仍不清楚。在这项研究中，使用CD 36封闭抗体（抗CD 36）在出生后第8天，我们评估了新生儿全身内毒素（脂多糖; LPS）的挑战。我们使用转基因小鼠模型通过生物发光成像可视化TLR 2响应，所述转基因小鼠模型在鼠TLR 2启动子的转录控制下携带双报告系统荧光素酶/绿色荧光蛋白。抗-CD 36治疗改变了LPS诱导的新生儿脑中的炎症特征，导致炎性细胞因子水平和TLR 2和TLR 3介导的信号传导显著降低，干扰素调节因子3（IRF 3）通路不受影响。用抗CD 36处理LPS攻击的人未成熟小胶质细胞诱导TLR 2/TLR 3表达水平显著降低，而TLR 4和IRF 3表达不受影响，表明人和小鼠小胶质细胞中共有的CD 36调节机制。总的来说，我们的研究结果表明，阻断CD 36改变LPS诱导的小鼠和人类小胶质细胞的炎症特征，表明其在神经炎症微调中的作用。
Innate immune response in neonatal brain is associated with a robust microglial activation and induction of Toll-like Receptors (TLRs). To date, the role of the scavenger receptor CD36 in TLRs modulation, particularly TLR2 signaling, has been well established in adult brain. However, the crosstalk between TLR4, TLR2 and CD36 and its immunogenic influence in the neonatal brain remains unclear. In this study, using a CD36 blocking antibody (anti-CD36) at post-natal day 8, we evaluated the response of neonates to systemic endotoxin (lipopolysaccharide; LPS) challenge. We visualized the TLR2 response by bioluminescence imaging using the transgenic mouse model bearing the dual reporter system luciferase/green fluorescent protein under transcriptional control of a murine TLR2 promoter. The anti-CD36 treatment modified the LPS induced inflammatory profile in neonatal brains, causing a significant decrease in inflammatory cytokine levels and the TLR2 and TLR3 mediated signalling.The interferon regulatory factor 3 (IRF3) pathway remained unaffected. Treatment of the LPS-challenged human immature microglia with anti-CD36 induced a marked decrease in TLR2/TLR3 expression levels while TLR4 and IRF3 expression was not affected, suggesting the shared CD36 regulatory mechanisms in human and mouse microglia. Collectively, our results indicate that blocking CD36 alters LPS-induced inflammatory profile of mouse and human microglia, suggesting its role in fine-tuning of neuroinflammation.
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影响因子：
8.3
作者：
Nijboer, Cora H.;Heijnen, Cobi J.;Kavelaars, Annemieke
通讯作者：
Kavelaars, Annemieke
CD36 参与 PrP106-126 诱导的小胶质细胞激活
影响因子：
3.7
作者：
Kouadir M;Yang L;Tan R;Shi F;Lu Y;Zhang S;Yin X;Zhou X;Zhao D
通讯作者：
Zhao D
DOI：
10.1016/j.bbi.2017.05.020
发表时间：
2017-10
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Lalancette-Hébert M;Faustino J;Thammisetty SS;Chip S;Vexler ZS;Kriz J
通讯作者：
Kriz J
影响因子：
4.6
作者：
Ferracini M;Rios FJ;Pecenin M;Jancar S
通讯作者：
Jancar S
影响因子：
21.3
作者：
Rolls, Asya;Shechter, Ravid;Schwartz, Michal
通讯作者：
Schwartz, Michal