gene transcription within microglia and other cells. Microglia and proinflammatory signals include multiple positive loops of autocrine and paracrine amplification that contribute to persistent microglial activation in brain [3]. These findings are consistent with hypotheses that infections early in life impact overall life span [4,5] and that microglial activation contributes to age-associated neurodegenerative diseases [6]. These hypotheses suggest that systemic inflammatory responses contribute to chronic diseases. Although multiple toll-like receptors activate monocyte-microglial proinflammatory responses, most studies have modeled bacterial endotoxin-LPS-TLR4-induced brain responses. We hypothesized that toll-like receptor 3 (TLR3), a receptor that activates monocyte NF-κB transcription of proinflammatory cytokines in response to virus-like mRNA [7], would induce blood proinflammatory responses and brain neuroinflammation.
