BCG vaccination-induced emergency granulopoiesis provides rapid protection from neonatal sepsis.

BCG vaccination-induced emergency granulopoiesis provides rapid protection from neonatal sepsis.
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DOI:
10.1126/scitranslmed.aax4517
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发表时间:
2020-05-06
影响因子:
17.1
通讯作者:
Amenyogbe N
Amenyogbe N
中科院分区:
医学1区
文献类型:
--
作者:
Brook B;Harbeson DJ;Shannon CP;Cai B;He D;Ben-Othman R;Francis F;Huang J;Varankovich N;Liu A;Bao W;Bjerregaard-Andersen M;Schaltz-Buchholzer F;Sanca L;Golding CN;Larsen KL;Levy O;Kampmann B;EPIC Consortium;Tan R;Charles A;Wynn JL;Shann F;Aaby P;Benn CS;Tebbutt SJ;Kollmann TR;Amenyogbe N

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新生儿败血症死亡仍然是数百万人的严重威胁。在接种后3天内,卡介苗(BCG)接种可以降低新生儿败血症的死亡率,但这种快速保护的潜在机制尚不清楚。我们发现,卡介苗也是保护新生儿多微生物败血症的小鼠模型,在那里它诱导粒细胞集落刺激因子(G-CSF)在数小时内的管理。这是必要的,足以驱动紧急粒细胞生成(EG),导致中性粒细胞显着增加。中性粒细胞的这种增加直接和定量地负责保护免于败血症。BCG给药后EG的快速诱导也发生在三个独立的人类新生儿队列中。
Death from sepsis in the neonatal period remains a serious threat for millions. Within 3 days of administration, bacille Calmette-Guérin (BCG) vaccination can reduce mortality from neonatal sepsis in human newborns, but the underlying mechanism for this rapid protection is unknown. We found that BCG was also protective in a mouse model of neonatal polymicrobial sepsis, where it induced granulocyte colony-stimulating factor (G-CSF) within hours of administration. This was necessary and sufficient to drive emergency granulopoiesis (EG), resulting in a marked increase in neutrophils. This increase in neutrophils was directly and quantitatively responsible for protection from sepsis. Rapid induction of EG after BCG administration also occurred in three independent cohorts of human neonates.
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