PMID:20441518

Citation	Oosting, M, Berende, A, Sturm, P, Ter Hofstede, HJ, de Jong, DJ, Kanneganti, TD, van der Meer, JW, Kullberg, BJ, Netea, MG and Joosten, LA (2010) Recognition of Borrelia burgdorferi by NOD2 is central for the induction of an inflammatory reaction. J. Infect. Dis. 201:1849-58
Abstract	Toll-like receptor 2 (TLR2) plays an important role in the recognition of Borrelia bacteria, the causative agent of Lyme disease, but the existence and importance of additional receptors in this process has been hypothesized. In the present study, we confirmed the role played by TLR2 in the recognition of Borrelia bacteria but also demonstrated a crucial role for the intracellular peptidoglycan receptor NOD2 for sensing the spirochete. Cells from individuals who were homozygous for the loss-of-function mutation 3020insC in the NOD2 gene were defective with respect to cytokine release after stimulation with Borrelia species, and this was confirmed in peritoneal macrophages from mice lacking RICK, the adaptor molecule used by NOD2. In contrast, NOD1 played no major role in the recognition of Borrelia spirochetes. This raises the intriguing possibility that recognition of Borrelia spirochetes is exerted by TLR2 in combination with NOD2 and that both receptors are necessary for an effective induction of cytokines by Borrelia species. The interplay between TLR2 and NOD2 might not only be necessary for the induction of a proper immune response but may also contribute to inflammatory-induced pathology.
Links	PubMed Online version:10.1086/652871
Keywords	Animals; Borrelia burgdorferi/immunology; Borrelia burgdorferi Group/immunology; Cells, Cultured; Humans; Inflammation; Leukocytes, Mononuclear/immunology; Leukocytes, Mononuclear/microbiology; Lyme Disease/immunology; Lyme Disease/pathology; Macrophages, Peritoneal/immunology; Macrophages, Peritoneal/microbiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Nod2 Signaling Adaptor Protein/immunology; Toll-Like Receptor 2/immunology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:NOD2		GO:0002720: positive regulation of cytokine production involved in immune response	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Figure 5. Effectiveness of NOD2 to produce cytokines as an immune response to Borrelia burgdorferi shown through experimentation of stimulated PBMCs.	complete CACAO 6508
HUMAN:TLR2	involved_in	GO:0002720: positive regulation of cytokine production involved in immune response	ECO:0000314: direct assay evidence used in manual assertion		P		Fig 2	complete

References

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