Fig. 3

Proposed summary of signaling mechanisms in MO3.13 human oligodendrocytes in response to B. burgdorferi. Activation of RTKs (EGFR/FGFR/PDGFR) by ligand-independent mechanisms, as mediated through GPCR or integrins, leads to phosphorylation of the intracellular domains of RTK. This leads to docking of proteins such as src, phospholipase Cγ (PLCγ) and others, which in turn activate downstream pathways like MAPK and MEK/ERK in particular. Significant activation of MEK/ERK, along with contribution from other MAPK and NFkB, leads to production of inflammatory mediators. We have demonstrated previously that MEK/ERK activation upregulates p53 and mitochondrial-mediated apoptosis in oligodendrocytes. The RTKs, for the sake of simplicity, are depicted as a single entity, although they are three separate receptors. Also, for the sake of illustration, they are surface located, although some could be trafficked internally [30]. B. burgdorferi can bind integrins, which could transactivate RTKs. It also has well-known ligands to bind to TLR2 or TLR5. Although gram negative, it does not possess a typical LPS (which binds to TLR4) but rather a LOS. However, TLR2, TLR4, and TLR5 play minimal roles in induction of oligodendrocyte inflammatory mediators, as shown in this study. Thickness of the lines/arrows indicates signal strength. Dashed lines/arrows indicate unknown possibilities, while dashed and dotted lines/arrows indicate additional likely signaling mechanisms. Adapted from Parthasarathy and Philipp [7], by permission