A Staphylococcus pro-apoptotic peptide induces acute exacerbation of pulmonary fibrosis
A Staphylococcus pro-apoptotic peptide induces acute exacerbation of pulmonary fibrosis
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DOI：
10.1038/s41467-020-15344-3
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发表时间：
2020-03-24
影响因子：
16.6
通讯作者：
Gabazza, Esteban C.
中科院分区：
文献类型：
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作者：
D'Alessandro-Gabazza, Corina N.;Kobayashi, Tetsu;Gabazza, Esteban C.
特发性肺纤维化（IPF）是一种病因不明的慢性致死性疾病;然而，肺泡上皮细胞凋亡在疾病进展中起作用。这种难治性疾病与肺部葡萄球菌和链球菌丰度增加有关，但它们在疾病发病机制中的作用仍然难以捉摸。在这里，我们报告说，尼泊尔葡萄球菌释放corisin，一种肽保守在不同的葡萄球菌，诱导肺上皮细胞凋亡。在小鼠中，在肺内滴注corisin或在肺部感染携带corisin的S. nepalensis与未处理的小鼠或用缺乏corisin的细菌感染的小鼠相比。相应地，与没有疾病恶化的患者相比，在具有急性恶化的人IPF患者中肺corisin水平显著增加。我们的研究结果表明，细菌脱落corisin参与了IPF的急性加重，从而深入了解了肺纤维化中葡萄球菌升高的分子基础。
Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal disease of unknown etiology; however, apoptosis of lung alveolar epithelial cells plays a role in disease progression. This intractable disease is associated with increased abundance of Staphylococcus and Streptococcus in the lungs, yet their roles in disease pathogenesis remain elusive. Here, we report that Staphylococcus nepalensis releases corisin, a peptide conserved in diverse staphylococci, to induce apoptosis of lung epithelial cells. The disease in mice exhibits acute exacerbation after intrapulmonary instillation of corisin or after lung infection with corisin-harboring S. nepalensis compared to untreated mice or mice infected with bacteria lacking corisin. Correspondingly, the lung corisin levels are significantly increased in human IPF patients with acute exacerbation compared to patients without disease exacerbation. Our results suggest that bacteria shedding corisin are involved in acute exacerbation of IPF, yielding insights to the molecular basis for the elevation of staphylococci in pulmonary fibrosis.