Elsner Rebecca A, Hastey Christine J, Olsen Kimberly J, Baumgarth Nicole
Center for Comparative Medicine, University of California, Davis, Davis, California, United States of America; Microbiology Graduate Group, University of California, Davis, Davis, California, United States of America.
Center for Comparative Medicine, University of California, Davis, Davis, California, United States of America.
PLoS Pathog. 2015 Jul 2;11(7):e1004976. doi: 10.1371/journal.ppat.1004976. eCollection 2015 Jul.
Lyme Disease caused by infection with Borrelia burgdorferi is an emerging infectious disease and already by far the most common vector-borne disease in the U.S. Similar to many other infections, infection with B. burgdorferi results in strong antibody response induction, which can be used clinically as a diagnostic measure of prior exposure. However, clinical studies have shown a sometimes-precipitous decline of such antibodies shortly following antibiotic treatment, revealing a potential deficit in the host's ability to induce and/or maintain long-term protective antibodies. This is further supported by reports of frequent repeat infections with B. burgdorferi in endemic areas. The mechanisms underlying such a lack of long-term humoral immunity, however, remain unknown. We show here that B. burgdorferi infected mice show a similar rapid disappearance of Borrelia-specific antibodies after infection and subsequent antibiotic treatment. This failure was associated with development of only short-lived germinal centers, micro-anatomical locations from which long-lived immunity originates. These showed structural abnormalities and failed to induce memory B cells and long-lived plasma cells for months after the infection, rendering the mice susceptible to reinfection with the same strain of B. burgdorferi. The inability to induce long-lived immune responses was not due to the particular nature of the immunogenic antigens of B. burgdorferi, as antibodies to both T-dependent and T-independent Borrelia antigens lacked longevity and B cell memory induction. Furthermore, influenza immunization administered at the time of Borrelia infection also failed to induce robust antibody responses, dramatically reducing the protective antiviral capacity of the humoral response. Collectively, these studies show that B. burgdorferi-infection results in targeted and temporary immunosuppression of the host and bring new insight into the mechanisms underlying the failure to develop long-term immunity to this emerging disease threat.
由伯氏疏螺旋体感染引起的莱姆病是一种新出现的传染病，并且已经是美国目前最常见的媒介传播疾病。与许多其他感染类似，伯氏疏螺旋体感染会诱导强烈的抗体反应，这在临床上可作为既往接触的诊断指标。然而，临床研究表明，抗生素治疗后不久，此类抗体有时会急剧下降，这揭示了宿主诱导和/或维持长期保护性抗体能力的潜在缺陷。流行地区频繁出现伯氏疏螺旋体重复感染的报告进一步支持了这一点。然而，这种缺乏长期体液免疫的潜在机制仍然未知。我们在此表明，感染伯氏疏螺旋体的小鼠在感染及随后的抗生素治疗后，伯氏疏螺旋体特异性抗体也会迅速消失。这种失败与仅短暂存在的生发中心的形成有关，生发中心是产生长期免疫力的微解剖位置。这些生发中心显示出结构异常，并且在感染数月后未能诱导记忆B细胞和长寿浆细胞的产生，使得小鼠易受同一菌株的伯氏疏螺旋体再次感染。无法诱导长期免疫反应并非由于伯氏疏螺旋体免疫原性抗原的特殊性质，因为针对T细胞依赖性和T细胞非依赖性伯氏疏螺旋体抗原的抗体都缺乏持久性且无法诱导B细胞记忆。此外，在伯氏疏螺旋体感染时进行流感疫苗接种也未能诱导出强烈的抗体反应，显著降低了体液反应的抗病毒保护能力。总的来说，这些研究表明，伯氏疏螺旋体感染会导致宿主有针对性的、暂时的免疫抑制，并为未能对这种新出现的疾病威胁产生长期免疫力的潜在机制带来了新的见解。
