sTREM-1 promotes the phagocytic function of microglia to induce hippocampus damage via the PI3K–AKT signaling pathway

Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a soluble form of TREM-1 released during inflammation. Elevated sTREM-1 levels have been found in neuropsychiatric systemic lupus erythematosus (NPSLE) patients; yet, the exact mechanisms remain unclear. This study investigated the role of sTREM-1 in brain damage and its underlying mechanism. The sTREM-1 recombinant protein (2.5 μg/3 μL) was injected into the lateral ventricle of C57BL/6 female mice. After intracerebroventricular (ICV) injection, the damage in hippocampal neurons increased, and the loss of neuronal synapses and activation of microglia increased compared to the control mice (treated with saline). In vitro. after sTREM-1 stimulation, the apoptosis of BV2 cells decreased, the polarization of BV2 cells shifted to the M1 phenotype, the phagocytic function of BV2 cells significantly improved, while the PI3K–AKT signal pathway was activated in vivo and in vitro. PI3K–AKT pathway inhibitor LY294002 reversed the excessive activation and phagocytosis of microglia caused by sTREM-1 in vivo and in vitro, which in turn improved the hippocampus damage. These results indicated that sTREM-1 activated the microglial by the PI3K–AKT signal pathway, and promoted its excessive phagocytosis of the neuronal synapse, thus inducing hippocampal damage. sTREM-1 might be a potential target for inducing brain lesions.