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- Title
Toll-Like Receptor 2–Mediated Autophagy Promotes Microglial Cell Death by Modulating the Microglial M1/M2 Phenotype.
- Authors
Ma, Kun; Guo, Jingjing; Wang, Guan; Ni, Qiuying; Liu, Xinjie
- Abstract
Toll-like receptor 2 (TLR2) regulates the innate immune response of microglia during infection via autophagy. Microglial M1/M2 phenotypic switching after infection could serve as a novel pathogenic mechanism for cerebral infection. Hence, it has important implications for the damage and restoration of neurological function. However, the effect of TLR2-mediated autophagic signaling on microglial phenotypic transition remains unclear. Therefore, we investigated the mechanisms of TLR2-mediated autophagic signaling in the regulation of microglial M1/M2 phenotypes. Using Western blot analysis and immunofluorescence, increased autophagy was observed in peptidoglycan (PGN)-stimulated BV2 cells, while reduced autophagy was observed in TLR2-KO cells. In contrast to the TLR2 antagonist CU-CPT22 group, increased autophagy was observed in the presence of the TLR2 agonist Pam3CSK4, which was associated with a significant increase in expression levels of M1 phenotype biomarkers (CD86, TNF-α, IL-6), higher levels of apoptosis, and decreased expression levels of M2 markers (CD206, IL-10, Arg-1). In the TLR2-KO mice, the expression levels of autophagy-related proteins in CD11b+ cells were lower than those in CD11b+ cells in the PGN-injected wild-type mice, and neuronal apoptosis was also reduced, but there were no significant differences compared to the control group. Collectively, our study demonstrates that the inhibition of autophagy or the absence of TLR2 induces microglial polarization towards the M2 phenotype, promotes microglial survival alone, and alleviates the development of neuroinflammation. In summary, TLR2-mediated autophagic signaling contributes to regulating the inflammatory response to activate microglial M1/M2 switching, which affects microglial survival after infection.
- Subjects
TOLL-like receptors; CELL death; WESTERN immunoblotting; PHENOTYPES
- Publication
Inflammation, 2020, Vol 43, Issue 2, p701
- ISSN
0360-3997
- Publication type
Article
- DOI
10.1007/s10753-019-01152-5