Activation of innate host defense mechanisms by Borrelia.
Borrelia is the causative agent of Lyme disease, a widespread disease with important health consequences. Immune-mediated mechanisms are believed to play a major role in both host defense and in late complications of Lyme disease. Recognition of Borrelia and the initial activation of the innate immune system are important for host defense, as well as modulation of adaptive responses. Several classes of pattern recognition receptors (PRRs) have been suggested to be involved in the recognition of Borrelia: Toll-like receptors (TLRs), NOD-like receptors (NLRs) and C-type lectin receptors (CLRs). TLR2 has been found to be the most important receptor of the TLRs. The intracellular receptor NOD2, a member of the NLRs, might also play an important role in recognition. Mannose receptor is also involved in Borrelia recognition, but little is known about other CLRs such as dectin-1. After PRRs have recognized Borrelia, a signaling cascade is induced that leads to transcription of NF-kappaB, resulting in the production of pro-inflammatory cytokines. Understanding these pathways provides not only a better insight into the pathogenesis, but also provides potential, novel, therapeutic targets during active disease or post-infection complications.
Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Anneleen
A
Berende
Marije
M
Oosting
Bart-Jan
BJ
Kullberg
Mihai G
MG
Netea
Leo A B
LA
Joosten
D000818:Animals; D001898:Borrelia / Q000276:immunology*; D004199:Disease Vectors; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D008193:Lyme Disease / Q000276:immunology / Q000382:microbiology / Q000635:transmission; D015398:Signal Transduction / Q000276:immunology