Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Brazilian Ministry of Health, Salvador, Brazil.
Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut.
Am J Trop Med Hyg. 2019 Sep;101(3):585-589. doi: 10.4269/ajtmh.19-0160.
Leptospirosis is the leading cause of zoonotic morbidity and mortality globally, yet little is known about the immune mechanisms that may contribute to pathogenesis and severe disease. Although neutrophils are a key component of early immune responses to infection, they have been associated with tissue damage and inflammation in some febrile infections. To assess whether neutrophils contribute to the pathogenesis observed in severe leptospirosis, we quantitated levels of neutrophil activation markers in patients with varying disease severities. Hospitalized leptospirosis patients had significantly higher levels of toll-like receptors 2 and 4 (TLR2 and TLR4, respectively) on peripheral neutrophils than healthy controls, with the highest levels detected in patients with organ dysfunction. We observed no significant differences in other neutrophil baseline activation markers (CD62L and CD11b) or activation capacity (CD62L and CD11b levels following stimulation), regardless of disease severity. Our results provide preliminary evidence supporting the hypothesis that higher initial bacterial loads or inadequate or delayed neutrophil responses, rather than TLR-driven inflammation, may drive severe disease outcomes.
钩端螺旋体病是全球导致动物源性发病和死亡的主要原因，但对于可能导致发病机制和严重疾病的免疫机制知之甚少。虽然中性粒细胞是感染后早期免疫反应的关键组成部分，但在一些发热感染中，它们与组织损伤和炎症有关。为了评估中性粒细胞是否导致严重钩端螺旋体病中观察到的发病机制，我们定量检测了不同疾病严重程度患者的中性粒细胞激活标志物水平。与健康对照组相比，住院钩端螺旋体病患者外周血中性粒细胞上的 toll 样受体 2 和 4（分别为 TLR2 和 TLR4）水平显著升高，在有器官功能障碍的患者中检测到的水平最高。无论疾病严重程度如何，我们都没有观察到其他中性粒细胞基线激活标志物（CD62L 和 CD11b）或激活能力（刺激后 CD62L 和 CD11b 水平）存在显著差异。我们的结果提供了初步证据，支持以下假说：较高的初始细菌负荷或不足或延迟的中性粒细胞反应，而不是 TLR 驱动的炎症，可能导致严重疾病的结果。
