期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：17
页码：5491-5496
DOI：10.1073/pnas.1502561112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceElevated levels of cholesterol and other lipid abnormalities are common diseases of adults. Cholesterol is an essential nutrient for Borrelia. To test whether increased levels of cholesterol could affect the infection with Borrelia, we used two types of mice with different deficiencies in cholesterol transport that result in increased cholesterol levels and infected them with two species of Borrelia. Infection with the agent of Lyme disease resulted in higher severity, increased number of bacteria in the joints, and ankle swelling. The higher mortality found in infections with relapsing-fever Borrelia was associated with an apolipoprotein E deficiency and was independent of cholesterol levels. Elevated serum lipids are common diseases that could be a risk factor for increased severity in Lyme disease. The Lyme disease (Borrelia burgdorferi) and relapsing-fever (Borrelia hispanica) agents have distinct infection courses, but both require cholesterol for growth. They acquire cholesterol from the environment and process it to form cholesterol glycolipids that are incorporated onto their membranes. To determine whether higher levels of serum cholesterol could enhance the organ burdens of B. burgdorferi and the spirochetemia of B. hispanica in laboratory mice, apolipoprotein E (apoE)-deficient and low-density lipoprotein receptor (LDLR)-deficient mice that produce large amounts of serum cholesterol were infected with both spirochetes. Both apoE- and LDLR-deficient mice infected with B. burgdorferi had an increased number of spirochetes in the joints and inflamed ankles compared with the infected wild-type (WT) mice, suggesting that mutations in cholesterol transport that result in high serum cholesterol levels can affect the pathogenicity of B. burgdorferi. In contrast, elevated serum cholesterol did not lead to an increase in the spirochetemia of B. hispanica. In the LDLR-deficient mice, the course of infection was indistinguishable from the WT mice. However, infection of apoE-deficient mice with B. hispanica resulted in a longer spirochetemia and increased mortality. Together, these results argue for the apoE deficiency, and not hypercholesterolemia, as the cause for the increased severity with B. hispanica. Serum hyperlipidemias are common human diseases that could be a risk factor for increased severity in Lyme disease.
