Lyme disease, caused by infection with the spirochetal pathogen Borrelia burgdorferi, affects over 400,000 individuals in the United States annually. Lyme disease is often accompanied by debilitating chronic inflammation and autoimmunity that can last for years and is a significant health burden to the public and military Service Members who reside in Lyme-endemic areas. However, the mechanism of infection-induced autoimmunity is not well understood. Recent studies have shown that during replication, Borrelia burgdorferi shed cell wall components, called peptidoglycan. These peptidoglycan fragments are detectible in joint fluid from patients with Lyme arthritis, many who had received months of antibiotic therapy. Bacterial peptidoglycan is a well-studied immune adjuvant that induces an inflammatory response to vaccine targets, or immunogens. In addition, peptidoglycan from other organisms is a key component of adjuvants used to induce autoimmunity in animal models of rheumatoid arthritis and multiple sclerosis. We hypothesize that peptidoglycan fragments shed during Borrelia burgorferi infection may activate components of the innate and adaptive immune system to induce dysregulated response to infection and autoimmunity.

The Principal Investigator (PI) is an early-career scientist whose research focus is on elucidating the mechanisms of Lyme infection-induced autoimmunity. Although autoimmunity in humans infected with Borrelia burgdorferi has been well-characterized, no animal models of infection-induced autoimmunity exist for Lyme disease research. This award will advance the PI’s career and the field by assisting in development of new animal models of autoimmunity that are critically needed to better understand the relationship between Borrelia burgdorferi infection, chronic inflammation, and autoimmunity. A potential effect of the proposed research is a better understanding of how chronic inflammation and autoimmunity develop in some patients with Lyme disease, thereby providing promising therapeutic targets to reduce or eliminate chronic inflammation and tissue damage that can persist for many years after treatment with antibiotic therapy.