Unit for Research on Emergent and Tropical Infectious Diseases (URMITE), CNRS-IRD UMR 6236, Faculty of Medicine, University of the Mediterranean, Marseille, France.
PLoS One. 2010 Jan 1;5(1):e8547. doi: 10.1371/journal.pone.0008547.
Brill-Zinsser disease, the relapsing form of epidemic typhus, typically occurs in a susceptible host years or decades after the primary infection; however, the mechanisms of reactivation and the cellular reservoir during latency are poorly understood. Herein we describe a murine model for Brill-Zinsser disease, and use PCR and cell culture to show transient rickettsemia in mice treated with dexamethasone >3 months after clinical recovery from the primary infection. Treatment of similarly infected mice with cyclosporine failed to produce recrudescent bacteremia. Therapy with doxycycline for the primary infection prevented recrudescent bacteremia in most of these mice following treatment with dexamethasone. Rickettsia prowazekii (the etiologic agent of epidemic typhus) was detected by PCR, cell culture, and immunostaining methods in murine adipose tissue, but not in liver, spleen, lung, or central nervous system tissues of mice 4 months after recovery from the primary infection. The lungs of dexamethasone-treated mice showed impaired expression of beta-defensin transcripts that may be involved in the pathogenesis of pulmonary lesions. In vitro, R. prowazekii rickettsiae infected and replicated in the murine adipocyte cell line 3T3-L1. Collectively these data suggest a role for adipose tissue as a potential reservoir for dormant infections with R. prowazekii.
布鲁氏-津塞二氏病是流行性斑疹伤寒的复发性形式，通常发生在初次感染后数年或数十年易感宿主；然而，再激活的机制和潜伏期间的细胞储库仍知之甚少。在此，我们描述了一种用于布鲁氏-津塞二氏病的小鼠模型，并通过 PCR 和细胞培养显示，在初次感染临床康复>3 个月后用地塞米松治疗的小鼠中存在短暂的立克次体血症。用环孢菌素治疗类似感染的小鼠未能产生复发性菌血症。对这些小鼠中的大多数进行初次感染的强力霉素治疗可预防在用地塞米松治疗后发生复发性菌血症。通过 PCR、细胞培养和免疫染色方法在初次感染后 4 个月的小鼠脂肪组织中检测到了流行性斑疹伤寒的病原体（普氏立克次体），但在肝脏、脾脏、肺或中枢神经系统组织中未检测到。用地塞米松治疗的小鼠的肺部显示出β-防御素转录物的表达受损，这可能与肺部病变的发病机制有关。在体外，R. prowazekii 立克次体感染并复制了小鼠脂肪细胞系 3T3-L1。这些数据共同表明脂肪组织可能是潜伏性感染 R. prowazekii 的潜在储库。
