Toledo Alvaro, Monzón Javier D, Coleman James L, Garcia-Monco Juan C, Benach Jorge L
Department of Molecular Genetics and Microbiology and.
Department of Molecular Genetics and Microbiology and New York State Department of Health, Center for Infectious Diseases, Stony Brook University, Stony Brook, NY 11794.
Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):5491-6. doi: 10.1073/pnas.1502561112. Epub 2015 Apr 13.
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.
莱姆病（伯氏疏螺旋体）和回归热（西班牙疏螺旋体）病原体具有不同的感染过程，但二者生长均需要胆固醇。它们从环境中获取胆固醇并将其加工形成胆固醇糖脂，后者整合到细胞膜上。为了确定血清胆固醇水平升高是否会增加实验室小鼠体内伯氏疏螺旋体的器官负荷以及西班牙疏螺旋体的螺旋体血症，研究人员用这两种螺旋体感染了能产生大量血清胆固醇的载脂蛋白E（apoE）缺陷型和低密度脂蛋白受体（LDLR）缺陷型小鼠。与感染的野生型（WT）小鼠相比，感染伯氏疏螺旋体的apoE缺陷型和LDLR缺陷型小鼠关节和发炎脚踝处的螺旋体数量均增加，这表明导致血清胆固醇水平升高的胆固醇转运突变会影响伯氏疏螺旋体的致病性。相比之下，血清胆固醇升高并未导致西班牙疏螺旋体的螺旋体血症增加。在LDLR缺陷型小鼠中，感染过程与WT小鼠并无差异。然而，用西班牙疏螺旋体感染apoE缺陷型小鼠会导致螺旋体血症持续时间延长且死亡率增加。总之，这些结果表明apoE缺陷而非高胆固醇血症是导致西班牙疏螺旋体感染严重程度增加的原因。血清高脂血症是常见的人类疾病，可能是莱姆病严重程度增加的一个危险因素。
