Larsson Christer, Lundqvist Jenny, van Rooijen Nico, Bergström Sven
Umeå University, Department of Molecular Biology and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå, Sweden.
PLoS Negl Trop Dis. 2009 Sep 29;3(9):e522. doi: 10.1371/journal.pntd.0000522.
Louse-borne relapsing fever (LBRF) borreliosis is caused by Borrelia recurrentis, and it is a deadly although treatable disease that is endemic in the Horn of Africa but has epidemic potential. Research on LBRF has been severely hampered because successful infection with B. recurrentis has been achieved only in primates (i.e., not in other laboratory or domestic animals). Here, we present the first non-primate animal model of LBRF, using SCID (-B, -T cells) and SCID BEIGE (-B, -T, -NK cells) immunocompromised mice. These animals were infected with B. recurrentis A11 or A17, or with B. duttonii 1120K3 as controls. B. recurrentis caused a relatively mild but persistent infection in SCID and SCID BEIGE mice, but did not proliferate in NUDE (-T) and BALB/c (wild-type) mice. B. duttonii was infectious but not lethal in all animals. These findings demonstrate that the immune response can limit relapsing fever even in the absence of humoral defense mechanisms. To study the significance of phagocytic cells in this context, we induced systemic depletion of such cells in the experimental mice by injecting them with clodronate liposomes, which resulted in uncontrolled B. duttonii growth and a one-hundred-fold increase in B. recurrentis titers in blood. This observation highlights the role of macrophages and other phagocytes in controlling relapsing fever infection. B. recurrentis evolved from B. duttonii to become a primate-specific pathogen that has lost the ability to infect immunocompetent rodents, probably through genetic degeneration. Here, we describe a novel animal model of B. recurrentis based on B- and T-cell-deficient mice, which we believe will be very valuable in future research on LBRF. Our study also reveals the importance of B-cells and phagocytes in controlling relapsing fever infection.
虱传回归热（LBRF）疏螺旋体病由回归热疏螺旋体引起，是一种虽可治疗但致命的疾病，在非洲之角为地方病且有流行潜力。对LBRF的研究受到严重阻碍，因为仅在灵长类动物（即不在其他实验动物或家畜中）实现了回归热疏螺旋体的成功感染。在此，我们展示了首个LBRF非灵长类动物模型，使用严重联合免疫缺陷（-B、-T细胞）和严重联合免疫缺陷米色（-B、-T、-NK细胞）免疫受损小鼠。这些动物感染回归热疏螺旋体A11或A17，或感染达顿疏螺旋体1120K3作为对照。回归热疏螺旋体在严重联合免疫缺陷和严重联合免疫缺陷米色小鼠中引起相对轻微但持续的感染，但在裸鼠（-T）和BALB/c（野生型）小鼠中不增殖。达顿疏螺旋体在所有动物中具有传染性但不致命。这些发现表明，即使在缺乏体液防御机制的情况下，免疫反应也能限制回归热。为研究吞噬细胞在此背景下的意义，我们通过给实验小鼠注射氯膦酸脂质体诱导此类细胞的全身耗竭，这导致达顿疏螺旋体不受控制地生长以及回归热疏螺旋体血液滴度增加一百倍。这一观察结果突出了巨噬细胞和其他吞噬细胞在控制回归热感染中的作用。回归热疏螺旋体从达顿疏螺旋体进化而来，可能通过基因退化成为一种灵长类特异性病原体，已失去感染免疫健全啮齿动物的能力。在此，我们描述了一种基于B细胞和T细胞缺陷小鼠的回归热疏螺旋体新型动物模型，我们认为这在未来LBRF研究中将非常有价值。我们的研究还揭示了B细胞和吞噬细胞在控制回归热感染中的重要性。
