Fatal Pertussis in the Neonatal Mouse Model Is Associated with Pertussis Toxin-Mediated Pathology beyond the Airways
Fatal Pertussis in the Neonatal Mouse Model Is Associated with Pertussis Toxin-Mediated Pathology beyond the Airways
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DOI：
10.1128/iai.00355-17
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发表时间：
2017-11-01
影响因子：
3.1
通讯作者：
Carbonetti, Nicholas H.
中科院分区：
文献类型：
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作者：
Scanlon, Karen M.;Snyder, Yael G.;Carbonetti, Nicholas H.
在婴儿中，百日咳杆菌可引起严重的疾病，表现为明显的白细胞增多、肺动脉高压，甚至死亡。死亡的确切原因仍然未知，也没有治疗暴发性百日咳的有效疗法。在这项研究中，新生小鼠模型的关键百日咳的特点，百日咳毒素（PT）的核心作用。PT促进新生小鼠而非成年小鼠的定植、白细胞增多、T细胞表型变化、全身病理学和死亡。令人惊讶的是，PT抑制了新生儿的肺部炎症病理，这一结果与在成年小鼠中观察到的PT促进的病理形成鲜明对比。感染PT缺陷型菌株可诱导新生小鼠发生严重的肺部炎症，但不会导致死亡，这表明这些小鼠的死亡与肺功能受损无关。在新生小鼠中还检测到肺部以外的感染传播，这可能有助于观察到的PT全身效应。我们认为是百日咳毒素的全身活性而不是肺部病理学促进了重症百日咳的死亡率。此外，我们观察到新生小鼠之间的感染传播，B的首次报告。百日咳在小鼠中的传播。该模型将是一个有价值的工具，以调查百日咳发病机制的原因，并确定潜在的治疗方案，为关键的百日咳。
In infants, Bordetella pertussis can cause severe disease, manifested as pronounced leukocytosis, pulmonary hypertension, and even death. The exact cause of death remains unknown, and no effective therapies for treating fulminant pertussis exist. In this study, a neonatal mouse model of critical pertussis is characterized, and a central role for pertussis toxin (PT) is described. PT promoted colonization, leukocytosis, T cell phenotypic changes, systemic pathology, and death in neonatal but not adult mice. Surprisingly, PT inhibited lung inflammatory pathology in neonates, a result which contrasts dramatically with observed PT-promoted pathology in adult mice. Infection with a PT-deficient strain induced severe pulmonary inflammation but not mortality in neonatal mice, suggesting that death in these mice was not associated with impaired lung function. Dissemination of infection beyond the lungs was also detected in neonatal mice, which may contribute to the observed systemic effects of PT. We propose that it is the systemic activity of pertussis toxin and not pulmonary pathology that promotes mortality in critical pertussis. In addition, we observed transmission of infection between neonatal mice, the first report of B. pertussis transmission in mice. This model will be a valuable tool to investigate causes of pertussis pathogenesis and identify potential therapies for critical pertussis.