Innate immunity networks during infection with Borrelia burgdorferi.

The recognition of Borrelia species represents a complex process in which multiple components of the immune system are involved. In this review, we summarize the interplay between the host innate system and Borrelia spp., from the recognition by pattern recognition receptors (PRRs) to the induction of a complex network of proinflammatory mediators. Several PRR families are crucial for recognition of Borrelia spp., including Toll-like receptors (TLRs) and Nucleotide Oligomerization Domain (NOD)-like receptors (NLRs). TLR-2 is crucial for the recognition of outer surface protein (Osp)A from Borrelia spp. and together with TLR8 mediates phagocytosis of the microorganism and production of type I interferons. Intracellular receptors such as TLR7, TLR8 and TLR9 on the one hand and the NLR receptor NOD2 on the other hand, represent the second major recognition system of Borrelia. PRR-dependent signals induce the release of pro-inflammatory cytokines such as interleukin-1 and T-helper-derived cytokines, which are thought to mediate the inflammation during Lyme disease. Understanding the regulation of host defense mechanisms against Borrelia has the potential to lead to the discovery of novel immunotherapeutic targets to improve the therapy against Lyme disease.