Effect of Borrelia burgdorferi Outer Membrane Vesicles on Host Oxidative Stress Response

Abstract

Outer membrane vesicles (OMVs) are spherical bodies containing proteins and nucleic acids that are released by Gram-negative bacteria, including <i>Borrelia burgdorferi</i>, the causative agent of Lyme disease. The functional relationship between <i>B. burgdorferi</i> OMVs and host neuron homeostasis is not well understood. The objective of this study was to examine how <i>B. burgdorferi</i> OMVs impact the host cell environment. First, an in vitro model was established by co-culturing human BE2C neuroblastoma cells with <i>B. burgdorferi</i> B31. <i>B. burgdorferi</i> was able to invade BE2C cells within 24 h. Despite internalization, BE2C cell viability and levels of apoptosis remained unchanged, but resulted in dramatically increased production of MCP-1 and MCP-2 cytokines. Elevated secretion of MCP-1 has previously been associated with changes in oxidative stress. BE2C cell mitochondrial superoxides were reduced as early as 30 min after exposure to <i>B. burgdorferi</i> and OMVs. To rule out whether BE2C cell antioxidant response is the cause of decline in superoxides, superoxide dismutase 2 (SOD2) gene expression was assessed. SOD2 expression was reduced upon exposure to <i>B. burgdorferi</i>, suggesting that <i>B. burgdorferi</i> might be responsible for superoxide reduction. These results suggest that <i>B. burgdorferi</i> modulates cell antioxidant defense and immune system reaction in response to the bacterial infection. In summary, these results show that <i>B. burgdorferi</i> OMVs serve to directly counter superoxide production in BE2C neurons, thereby 'priming' the host environment to support <i>B. burgdorferi</i> colonization.