Absence of the lectin-like domain of thrombomodulin reduces HSV-1 lethality of mice with increased microglia responses

Meng Shan Tsai, Li Chiu Wang, Hua Lin Wu, Shun Fen Tzeng, Edward M. Conway, Sheng Min Hsu, Shun Hua Chen

研究成果: Article同行評審

摘要

Background: Herpes simplex virus 1 (HSV-1) can induce fatal encephalitis. Cellular factors regulate the host immunity to affect the severity of HSV-1 encephalitis. Recent reports focus on the significance of thrombomodulin (TM), especially the domain 1, lectin-like domain (TM-LeD), which modulates the immune responses to bacterial infections and toxins and various diseases in murine models. Few studies have investigated the importance of TM-LeD in viral infections, which are also regulated by the host immunity. Methods: In vivo studies comparing wild-type and TM-LeD knockout mice were performed to determine the role of TM-LeD on HSV-1 lethality. In vitro studies using brain microglia cultured from mice or a human microglia cell line to investigate whether and how TM-LeD affects microglia to reduce HSV-1 replication in brain neurons cultured from mice or in a human neuronal cell line. Results: Absence of TM-LeD decreased the mortality, tissue viral loads, and brain neuron apoptosis of HSV-1-infected mice with increases in the number, proliferation, and phagocytic activity of brain microglia. Moreover, TM-LeD deficiency enhanced the phagocytic activity of brain microglia cultured from mice or of a human microglia cell line. Co-culture of mouse primary brain microglia and neurons or human microglia and neuronal cell lines revealed that TM-LeD deficiency augmented the capacity of microglia to reduce HSV-1 replication in neurons. Conclusions: Overall, TM-LeD suppresses microglia responses to enhance HSV-1 infection.

原文English
文章編號66
期刊Journal of Neuroinflammation
19
發行號1
DOIs
出版狀態Published - 2022 12月

All Science Journal Classification (ASJC) codes

  • 神經科學 (全部)
  • 免疫學
  • 神經內科
  • 細胞與分子神經科學

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