Figure 1.

Extracellular and intracellular signaling pathways mediated by B. burgdorferi. Overview of the pathogen recognition receptors (PRRs) involved in the recognition and signaling in response to B. burgdorferi. Cell surface signaling is primarily mediated by TLR2/1 leading to pro-inflammatory cytokine production. Integrins and CD14 are known to recognize and internalize the spirochete but their role in intracellular signaling is not fully understood. Intracellular receptors located at the endosome, in particular TLR2/1, TLR7/8, and TLR9, are activated by different B. burgdorferi ligands and recruit adaptors such as MyD88 and/or TRIF to transduce signals for the activation of inflammatory cytokines and type I IFNs. The Nod2 receptor also plays a role in recognition of B. burgdorferi and in the induction of inflammatory responses, but it might have a dual regulatory role depending on the stage of infection. The inflammasome is likely to be involved, however, in vivo, it is unclear whether the inflammasome is required for the development of host responses to the pathogen.