Continuous injection of high-dose lipopolysaccharide modulates microglia polarization via TREM2 to alter the status of septic mice

Abstract Background Neuroinflammation of the central nervous system (CNS) is a prevalent syndrome of brain dysfunction secondary to severe sepsis and is regulated by microglia. Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) is known to have protective functions, which modulates microglia polarization to M2 type to reduce inflammatory responses and thereby improve cognition. Methods We examined the effect of TREM2 on the polarization state of microglia during the onset of neuroinflammation. After one week of lipopolysaccharide consecutive injection, immunofluorescence (IF) assays, hematoxylin-eosin (HE), electron microscopy and western blotting were used to visualize hippocampal sections in C57BL/6 mice to assess TREM2 release. In addition, microglia polarization was analyzed by Quantitative RT-PCR. Result Continuous injection of LPS for 7 days improved systemic inflammation and behavioral cognitive dysfunction in septic mice. Serial injection of LPS for 7 days attenuated neuroinflammation in septic mice. LPS could reduce the expression of TREM2, however IFN-β enhanced TREM2 expression. TREM2 regulated the conversion of the microglial M1 phenotype to M2 phenotype. Conclusion The aim of this study was to further investigate the interconnection between microglia polarization and TREM2 in the CNS. All evidence supports our hypothesis that IFN-β can modulate TREM2 expression to alter the polarization state of microglia and thereby reduce central neuroinflammation induced by sequential LPS injections. Trem2 can be used as a new target for neuroinflammation treatment.