Primary Human Microglia Are Phagocytically Active and Respond to With Upregulation of Chemokines and Cytokines.

The Lyme disease causing bacterium has an affinity for the central nervous system (CNS) and has been isolated from human cerebral spinal fluid by 18 days following tick bite. Signaling from resident immune cells of the CNS could enhance CNS penetration by and activated immune cells through the blood brain barrier resulting in multiple neurological complications, collectively termed neuroborreliosis. The ensuing symptoms of neurological impairment likely arise from a glial-driven, host inflammatory response to . To date, however, the mechanism by which the bacterium initiates neuroinflammation leading to neural dysfunction remains unclear. We hypothesized that dead and bacterial debris persist in the CNS in spite of antibiotic treatment and contribute to the continuing inflammatory response in the CNS. To test our hypothesis, cultures of primary human microglia were incubated with live, antibiotic-killed and antibiotic-killed sonicated to define the response of microglia to different forms of the bacterium. We demonstrate that primary human microglia treated with show increased expression of pattern recognition receptors and genes known to be involved with cytoskeletal rearrangement and phagocytosis including MARCO, SCARB1, PLA2, PLD2, CD14, and TLR3. In addition, we observed increased expression and secretion of pro-inflammatory mediators and neurotrophic factors such as IL-6, IL-8, CXCL-1, and CXCL-10. Our data also indicate that interacts with the cell surface of primary human microglia and may be internalized following this initial interaction. Furthermore, our results indicate that dead and sonicated forms of induce a significantly larger inflammatory response than live bacteria. Our results support our hypothesis and provide evidence that microglia contribute to the damaging inflammatory events associated with neuroborreliosis.