Live imaging of the innate immune response in neonates reveals differential TLR2 dependent activation patterns in sterile inflammation and infection

摘要: Activation of microglial cells in response to brain injury and/or immune stimuli is associated with a marked induction Toll-like receptors (TLRs). While adult brain, the contribution individual TLRs, including TLR2, pathophysiological cascades has been well established, their role and spatial temporal patterns immature are far less understood. To examine whether infectious sterile inflammatory trigger distinct TLR2-mediated innate responses, we used three models postnatal day 9 (P9) mice, model infection induced by systemic endotoxin injection two inflammation, intra-cortical IL-1β transient middle cerebral artery occlusion (tMCAO). We took advantage transgenic mouse bearing dual reporter system luciferase/GFP under transcriptional control murine TLR2 promoter (TLR2-luc-GFP) visualize living neonatal then determined neuroinflammation, activation leukocyte infiltration. show that physiological development vivo TLR2-luc signal undergoes ∼30-fold decline temporal-spatial changes during second third weeks. while robustly induces increases levels several cytokines chemokines, reduced after both tMCAO muted. Immunofluorescence revealed predominant source production all studied. Flow cytometry developmental CD11b+/CD45+ CD11b+/Ly6C+ cell populations, involvement monocyte lineage, but lack Ly6G+ neutrophils or CD3+ acutely injured brains. Cumulatively, our results suggest following PAMP DAMP - mediated inflammation brain.