Gene Expression Regulation in Brain Underlying Innate Immune Memory

As the brain’s resident immune cells, microglia upregulate inflammatory gene expression to promote immune functions. Following the response to early life infection, microglia can remain in a “primed” state in which a subsequent immune trigger produces a hyper-activation. Paradoxically, multiple repeated immune activating events can lead to tolerance, the suppression of immune gene expression and function. Both priming and tolerance represent a form of cellular memory that may be disrupted in neurodevelopmental disorders and is largely unexplored in microglia. We hypothesize that acute versus repeated immune activation engages expression of distinct sets of genes, leading to either microglial priming or tolerance. Using in vivo peripheral injections of low dose liposaccharide (LPS 500ug/kg intraperitoneal) to mimic bacterial infection in mice, we compared animals recievig 1, 2, 3, or 4 daily doses of LPS compared to Vehicle (PBS) controls. We examined tissue from three brain regions, the hippocampus, striatum and frotal cortex by RNAseq.