Abstract
The spirochete Borrelia burgdorferi is the agent of Lyme
disease, which causes central nervous system manifestations in up
to 20% of patients. We investigated the response of human brain
microglial cells, glial progenitors, neurons, astrocytes, as well as
peripheral blood monocytes to stimulation with B. burgdorferi. We
used oligoarrays to detect changes in the expression of genes
important for shaping adaptive and innate immune responses. We
found that stimulation with B. burgdorferi lysate increased the
expression of Toll-like receptors (TLRs) 1 and 2 in all cell types
except neurons. However, despite similarities in global gene
profiles of monocytes and microglia, only microglial cells
responded to the stimulation with a robust increase in HLA-DR,
HLA-DQ, and also coexpressed CD11-c, a dendritic cell marker. In
contrast, a large number of HLA-related molecules were repressed
at both the RNA and the protein levels in stimulated monocytes,
whereas secretion of IL-10 and TNF-> was strongly induced.
These results show that signaling through TLR1/2 in response to
B. burgdorferi can elicit opposite immunoregulatory effects in
blood and in brain immune cells, which could play a role in the
different susceptibility of these compartments to infection.
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