Infectious arthritis and immune dysregulation: lessons from Lyme disease

Purpose of review Borrelia burgdorferi colonization of the joints induces an inflammatory response, which in some individuals progresses to chronic arthritis. In this review, we discuss novel pathways that are implicated in disease development by modulating host defenses to B. burgdorferi infection. Recent findings The use of transgenic mice and gene expression analyses has revealed novel pathways involved in pathogenesis of Lyme disease. It is now clear that B. burgdorferi exploits an array of salivary gland proteins of the tick to evade immune responses in the mammalian host. The spirochete also modulates its surface protein profile upon infection and induces anti-inflammatory cytokines, favoring survival of the pathogen. The host defense involves toll-like receptors (TLRs), such as TLR2 and others, in B. burgdorferi recognition. To further dissect the genetic predisposition to treatment-refractory Lyme arthritis, HLA-DR transgenic mice have been used. Summary The cause and pathogenesis of Lyme arthritis are complex. Elucidating the mechanisms that govern this chronic inflammatory response will provide direct insights into other infectious arthritides and the development of novel therapeutic approaches against B. burgdorferi infection.