Involvement of macrophages in regulating Borrelia burgdorferi infection

Numerous in vitro studies have suggested that macrophages actively phagocytize Borrelia burgdorferi, the agent of Lyme disease, however; their role in clearance of these bacteria from infected animals has not been established. We evaluated the role of macrophages in regulating the hematogenous dissemination of B. burgdorferi in mice. Splenic and liver macrophages were eliminated by intravenous delivery of liposome-entrapped dichloromethylene diphosphonate (L-C12MDP). Results indicated that macrophage depletion had no influence on the development of infection as determined by immunoglobulin production and arthritis severity. PCR detection of B. burgdorferi DNA indicated the presence of spirochetes in ears, ankles, and hearts of all infected mice, with no significant differences observed in B. burgdorferi numbers from macrophage depleted or control animals. PCR analysis of blood from B. burgdorferi infected mice suggests that macrophage depletion might promote an early blood-borne spreading of B. burgdorferi, as mice treated with L-C12MDP expressed a clear early dissemination 5 days postinfection and, to a lesser extent, at 10 days following infection. However, in other experiments equivalent levels of B. burgdorferi were detected in blood of infected mice at different time points, regardless of the treatment they had received. In summary, depletion of macrophages from the liver and spleen does not influence the progression of Lyme disease pathology nor the abundance of spirochetes in tissues. Resident macrophages might play an important role in controlling spirochete dissemination in early stages of disease; however B. burgdorferi in later stages are able to restore their ability to disseminate to targeted tissues, possibly by migration through tissues rather than dissemination by blood.