Abstract

Outer membrane vesicles (OMVs) are spherical bodies containing proteins and nucleic acids that are released by Gram-negative bacteria, including Borrelia burgdorferi, the causative agent of Lyme disease. The functional relationship between B. burgdorferi OMVs and host neuron homeostasis is not well understood. The objective of this study was to examine how B. burgdorferi OMVs impact the host cell environment. First, an in vitro model was established by co-culturing human BE2C neuroblastoma cells with B. burgdorferi B31. B. burgdorferi 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 B. burgdorferi 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 B. burgdorferi, suggesting that B. burgdorferi might be responsible for superoxide reduction. These results suggest that B. burgdorferi modulates cell antioxidant defense and immune system reaction in response to the bacterial infection. In summary, these results show that B. burgdorferi OMVs serve to directly counter superoxide production in BE2C neurons, thereby ‘priming’ the host environment to support B. burgdorferi colonization.

Highlights

  • Lyme disease is the most common vector-borne disease in the United States and Europe [1,2].The causative agent of the disease, the spirochetal bacterium Borrelia burgdorferi, is transmitted through bites from ticks belonging to the genus Ixodes [3]

  • B. burgdorferi appeared to form an atypical round body-like morphology (Figure 2)

  • The results indicated that BE2C cell viability was not changed neuronal cytokines under co-culturing conditions has been reported to alter communication between significantly when untreated cells were compared with cells co-cultured with B. burgdorferi

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Summary

Introduction

Lyme disease is the most common vector-borne disease in the United States and Europe [1,2]. The causative agent of the disease, the spirochetal bacterium Borrelia burgdorferi, is transmitted through bites from ticks belonging to the genus Ixodes [3]. According to the Center for Disease Control, there are. 300,000 cases of Lyme disease annually, making it the most common tick-borne illness in the United. The prevalence and steady growth in Lyme disease cases makes this a pressing public health concern [5]. Lyme disease is a multi-system infection resulting in localized or disseminated acute or chronic symptoms such as erythema migrans, neurological or cardiac involvement, and arthritis [6].

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