Microglial cells are components of the immune system intrinsic to the central nervous system and they participate in the response induced by infection, aseptic inflammation, injury and/or neurodegeneration. These cells migrate to injury sites in response to chemoattractant agents that are produced under inflammatory circumstances. This response greatly depends on the expression and function of chemokine receptors, such as mFPR2, the MCP-1 receptor CCR2 and the fractalkine receptor CX3CR1 among others. In previous reports we demonstrated that peptidoglycan (PGN) derived from Staphylococcus aureus, a Toll like receptor 2 (TLR2) agonist, induced a considerable increase in the expression of the chemokine receptor mFPR2 in mice microglial cells.
In this work, we evaluate the role of TLR2 in the regulation of the expression and function of chemokine receptors important in the recruitment of phagocytes and neuroinflammation such as CCR2 and CX3CR1.
First of all, we observed by flow cytometry that systemic injection of PGN induces an increased recruitment of leukocytes to the central nervous system in C57BL/6 mice in comparison to animals injected with vehicle (p<0.05). On the other hand, in in vitro experiments we assessed either by RT-PCR and qRT-PCR that direct stimulation of a murine microglial cell line with PGN induced a gradual decrease of the chemokine receptors CCR2 and CX3CR1 gene expression throughout time (p<0.05).
Our results suggest that stimulation of TLR2 would induce recruitment of leukocytes to the central nervous system and regulation of chemokine receptors in microglial cells, which are key in the neuroinflammatory response. However, it is necessary to further investigate the precise mechanisms underlying this modulation and which consequences would have over this response.
