Temporal eicosanoid profiling of the inflammatory response to infection by the Lyme disease bacterium

Abstract

Lyme disease is caused by infection with the spirochete B. burgdorferi. If untreated, 60% of infected individuals will develop an arthritis characterized by the infiltration of macrophages and neutrophils into the infected joint. Eicosanoids play a critical role in recruiting innate immune cells during the development of arthritis; however, their role in the response to infection is poorly understood. To study the contribution of eicosanoids to infection response, we utilized a murine model of Lyme disease that recapitulates many of the pathological hallmarks of the human disease before spontaneously resolving. Susceptible C3H/HeJ mice were infected with B. burgdorferi, and joint tissue was removed at days 0, 3, 7, 10, 14, 17, 21, 24, 28 and 35 for histological and molecular analysis. Using LC‐MS/MS methodology that has the capability to identify and quantitate over 100 different eicosanoids, we detected over 30 different metabolites from COX, 5‐LO, 12‐LO, 15‐LO and CYP450s in the infected joints. Furthermore, we have identified temporal eicosanoid patterns that correlate with the pathological progression of infection. Application of this method may allow for the identification of lipid mediators with previously unappreciated functions in this as well as other disease models. This work was supported by the LIPID MAPS Large Scale Collaborative Grant GM069338, NIH AR052748 and 2T32DK007202‐32.