NOD2 contributes to the inflammatory responses of primary murine microglia and astrocytes to Staphylococcus aureus.

We have recently demonstrated that microglia and astrocytes express nucleotide-binding oligomerization domain-2 (NOD2), a novel cytosolic pattern recognition receptor for bacterial motifs, and we have shown that this intracellular receptor is essential for glial responses to Gram-negative pathogens. Here, we demonstrate that intact Staphylococcus aureus, a major Gram-positive causative agent of brain abscesses, activates the transcription factor NF-kappaB and is a potent stimulus for inflammatory cytokine production in primary murine microglia and astrocytes. Interestingly, we demonstrate that NOD2 is essential for maximal glial responses to intact S. aureus, but not cellular lysates. As such, this data indicates that NOD2 plays an important role in initiating inflammatory mediator production by resident brain cells following S. aureus infection and we suggest that this cytosolic receptor acts in conjunction with cell surface pattern recognition receptors to elicit maximal glial responses.