卡介苗接种诱导的紧急粒细胞生成可快速预防新生儿败血症。
BCG vaccination-induced emergency granulopoiesis provides rapid protection from neonatal sepsis.
作者信息
Brook Byron, Harbeson Danny J, Shannon Casey P, Cai Bing, He Daniel, Ben-Othman Rym, Francis Freddy, Huang Joe, Varankovich Natallia, Liu Aaron, Bao Winnie, Bjerregaard-Andersen Morten, Schaltz-Buchholzer Frederik, Sanca Lilica, Golding Christian N, Larsen Kristina Lindberg, Levy Ofer, Kampmann Beate, Tan Rusung, Charles Adrian, Wynn James L, Shann Frank, Aaby Peter, Benn Christine S, Tebbutt Scott J, Kollmann Tobias R, Amenyogbe Nelly
机构信息
Department of Experimental Medicine, University of British Columbia, 2775 Laurel Street, 10th Floor, Room 10117, Vancouver, BC V5Z 1M9, Canada.
PROOF Centre of Excellence, British Columbia, 10th floor, 1190 Hornby Street, Vancouver, BC V6Z 2K5, Canada.
出版信息
Sci Transl Med. 2020 May 6;12(542). doi: 10.1126/scitranslmed.aax4517.
Abstract
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.
摘要
新生儿期败血症导致的死亡对数以百万计的人来说仍然是一个严重威胁。在接种卡介苗（BCG）3天内，可降低人类新生儿因败血症导致的死亡率，但其快速发挥保护作用的潜在机制尚不清楚。我们发现，卡介苗在新生儿多微生物败血症小鼠模型中也具有保护作用，接种后数小时内可诱导产生粒细胞集落刺激因子（G-CSF）。这对于驱动紧急粒细胞生成（EG）是必要且充分的，从而导致中性粒细胞显著增加。中性粒细胞的这种增加直接且定量地起到了预防败血症的作用。在三个独立的人类新生儿队列中，接种卡介苗后也出现了EG的快速诱导。
相似文献
1
BCG vaccination-induced emergency granulopoiesis provides rapid protection from neonatal sepsis.卡介苗接种诱导的紧急粒细胞生成可快速预防新生儿败血症。
Sci Transl Med. 2020 May 6;12(542). doi: 10.1126/scitranslmed.aax4517.
2
Effect of stem cell factor with and without granulocyte colony-stimulating factor on neonatal hematopoiesis: in vivo induction of newborn myelopoiesis and reduction of mortality during experimental group B streptococcal sepsis.干细胞因子联合或不联合粒细胞集落刺激因子对新生儿造血的影响：在B族链球菌败血症实验中对新生骨髓生成的体内诱导及死亡率降低。
Blood. 1992 Jul 1;80(1):96-101.
3
Granulocyte-colony stimulating factor in neonatal sepsis with leukopenia: A prospective cohort study.粒细胞集落刺激因子用于新生儿败血症伴白细胞减少症：一项前瞻性队列研究。
J Pak Med Assoc. 2018 Nov;68(11):1613-1617.
4
Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor have differential effects on neonatal and adult neutrophil survival and function.粒细胞集落刺激因子和粒细胞-巨噬细胞集落刺激因子对新生儿和成人中性粒细胞的存活及功能有不同影响。
Pediatr Res. 2005 Jun;57(6):806-12. doi: 10.1203/01.PDR.0000156500.13600.B5. Epub 2005 Feb 17.
5
An IL-10/DEL-1 axis supports granulopoiesis and survival from sepsis in early life.IL-10/DEL-1 轴支持生命早期脓毒症中的粒细胞生成和存活。
Nat Commun. 2024 Jan 23;15(1):680. doi: 10.1038/s41467-023-44178-y.
6
A randomized, placebo-controlled trial of recombinant human granulocyte colony-stimulating factor administration in newborn infants with presumed sepsis: significant induction of peripheral and bone marrow neutrophilia.一项针对疑似脓毒症新生儿给予重组人粒细胞集落刺激因子的随机、安慰剂对照试验：显著诱导外周血和骨髓中性粒细胞增多。
Blood. 1994 Sep 1;84(5):1427-33.
7
Immediate Bacille Calmette-Guérin Vaccination to Neonates Requiring Perinatal Treatment at the Maternity Ward in Guinea-Bissau: A Randomized Controlled Trial.即刻接种卡介苗给需要在几内亚比绍妇产科病房进行围产期治疗的新生儿：一项随机对照试验。
J Infect Dis. 2021 Dec 1;224(11):1935-1944. doi: 10.1093/infdis/jiab220.
8
Preliminary report: rhG-CSF may reduce the incidence of neonatal sepsis in prolonged preeclampsia-associated neutropenia.初步报告：重组人粒细胞集落刺激因子（rhG-CSF）可能降低重度子痫前期相关中性粒细胞减少症患儿新生儿败血症的发生率。
Pediatrics. 1998 Nov;102(5):1107-11. doi: 10.1542/peds.102.5.1107.
9
Myeloid colony-stimulating factors: use in the newborn.髓系集落刺激因子：在新生儿中的应用。
Arch Pediatr Adolesc Med. 1999 Sep;153(9):984-8. doi: 10.1001/archpedi.153.9.984.
10
Effect of interleukin-11 with and without granulocyte colony-stimulating factor on in vivo neonatal rat hematopoiesis: induction of neonatal thrombocytosis by interleukin-11 and synergistic enhancement of neutrophilia by interleukin-11 + granulocyte colony-stimulating factor.白细胞介素-11单独及联合粒细胞集落刺激因子对新生大鼠体内造血的影响：白细胞介素-11诱导新生大鼠血小板增多，白细胞介素-11与粒细胞集落刺激因子联合使用可协同增强中性粒细胞增多。
Pediatr Res. 1993 Jul;34(1):56-61. doi: 10.1203/00006450-199307000-00014.
引用本文的文献
1
Long-term immune changes after COVID-19 and the effect of BCG vaccination and latent infections on disease severity.新冠病毒感染后的长期免疫变化以及卡介苗接种和潜伏感染对疾病严重程度的影响。
Clin Transl Immunology. 2025 Jun 27;14(7):e70041. doi: 10.1002/cti2.70041. eCollection 2025.
2
Immune mechanisms mediating the heterologous effects of BCG vaccination: a systematic review.介导卡介苗接种异源效应的免疫机制：一项系统综述
Front Immunol. 2025 May 19;16:1567111. doi: 10.3389/fimmu.2025.1567111. eCollection 2025.
3
FXR protects against neonatal sepsis by enhancing the immunosuppressive function of MDSCs.法尼醇X受体通过增强髓源性抑制细胞的免疫抑制功能来预防新生儿败血症。
Cell Mol Immunol. 2025 May 8. doi: 10.1038/s41423-025-01289-4.
4
Innate immune training in the neonatal response to sepsis.新生儿对败血症反应中的先天免疫训练
Mol Med. 2025 Apr 30;31(1):159. doi: 10.1186/s10020-025-01179-5.
5
G-CSF-Induced Emergency Granulopoiesis Modulates Neutrophil Effector Function in Mice.粒细胞集落刺激因子诱导的应急粒细胞生成调节小鼠中性粒细胞效应功能。
Stem Cell Rev Rep. 2025 May;21(4):1113-1126. doi: 10.1007/s12015-025-10885-w. Epub 2025 Apr 29.
6
Repurposing peripheral immunocytes of Bacillus Calmette Guerin-vaccinated melanoma patients to reveal preventive Alzheimer's disease mechanisms, possibly via the unfolded protein response.重新利用卡介苗接种的黑色素瘤患者的外周免疫细胞，以揭示预防性阿尔茨海默病机制，可能是通过未折叠蛋白反应。
J Alzheimers Dis Rep. 2025 Feb 10;9:25424823241309664. doi: 10.1177/25424823241309664. eCollection 2025 Jan-Dec.
7
Nurses' experiences in neonatal sepsis prevention and management: a qualitative cross-sectional study at selected hospitals in a metropolitan area.护士在新生儿败血症预防和管理方面的经验：在大都市地区选定医院进行的定性横断面研究。
BMC Health Serv Res. 2024 Oct 29;24(1):1298. doi: 10.1186/s12913-024-11811-5.
8
Precision adjuvants for pediatric vaccines.儿科疫苗的精准佐剂。
Sci Transl Med. 2024 Sep 4;16(763):eabq7378. doi: 10.1126/scitranslmed.abq7378.
9
The mark of success: The role of vaccine-induced skin scar formation for BCG and smallpox vaccine-associated clinical benefits.成功的标志：疫苗诱导的皮肤瘢痕形成在卡介苗和天花疫苗相关临床获益中的作用。
Semin Immunopathol. 2024 Aug 26;46(5):13. doi: 10.1007/s00281-024-01022-9.
10
BCG vaccination alters the epigenetic landscape of progenitor cells in human bone marrow to influence innate immune responses.BCG 疫苗接种改变了人类骨髓祖细胞中的表观遗传景观，从而影响先天免疫反应。
Immunity. 2024 Sep 10;57(9):2095-2107.e8. doi: 10.1016/j.immuni.2024.07.021. Epub 2024 Aug 16.
本文引用的文献
1
Licensed Bacille Calmette-Guérin (BCG) formulations differ markedly in bacterial viability, RNA content and innate immune activation.许可的卡介苗（BCG）制剂在细菌活力、RNA 含量和固有免疫激活方面有显著差异。
Vaccine. 2020 Feb 24;38(9):2229-2240. doi: 10.1016/j.vaccine.2019.11.060. Epub 2020 Jan 28.
2
Aetiology of invasive bacterial infection and antimicrobial resistance in neonates in sub-Saharan Africa: a systematic review and meta-analysis in line with the STROBE-NI reporting guidelines.撒哈拉以南非洲地区新生儿侵袭性细菌感染和抗菌药物耐药的病因学：一项基于 STROBE-NI 报告规范的系统评价和荟萃分析。
Lancet Infect Dis. 2019 Nov;19(11):1219-1234. doi: 10.1016/S1473-3099(19)30414-1. Epub 2019 Sep 12.
3
Chlorogenic Acid Inhibits BAFF Expression in Collagen-Induced Arthritis and Human Synoviocyte MH7A Cells by Modulating the Activation of the NF-B Signaling Pathway.绿原酸通过调控 NF-B 信号通路的激活抑制胶原诱导性关节炎和人滑膜细胞 MH7A 中 BAFF 的表达。
J Immunol Res. 2019 May 22;2019:8042097. doi: 10.1155/2019/8042097. eCollection 2019.
4
Anti-inflammatory activity of β-caryophyllene combined with docosahexaenoic acid in a model of sepsis induced by Staphylococcus aureus in mice.β-石竹烯与二十二碳六烯酸联合治疗金黄色葡萄球菌诱导脓毒症模型小鼠的抗炎活性。
J Sci Food Agric. 2019 Oct;99(13):5870-5880. doi: 10.1002/jsfa.9861. Epub 2019 Jul 11.
5
Pulegone inhibits inflammation via suppression of NLRP3 inflammasome and reducing cytokine production in mice.薄荷酮通过抑制 NLRP3 炎性小体和减少细胞因子产生来抑制炎症反应。
Immunopharmacol Immunotoxicol. 2019 Jun;41(3):420-427. doi: 10.1080/08923973.2019.1588292. Epub 2019 May 28.
6
Surveillance for incidence and etiology of early-onset neonatal sepsis in Soweto, South Africa.南非索韦托地区早发性新生儿败血症的发病和病因监测。
PLoS One. 2019 Apr 10;14(4):e0214077. doi: 10.1371/journal.pone.0214077. eCollection 2019.
7
A systems pharmacology workflow with experimental validation to assess the potential of anakinra for treatment of focal and segmental glomerulosclerosis.采用系统药理学工作流程并进行实验验证，评估阿那白滞素治疗局灶节段性肾小球硬化症的潜力。
PLoS One. 2019 Mar 28;14(3):e0214332. doi: 10.1371/journal.pone.0214332. eCollection 2019.
8
Dihydromyricetin Alleviates Sepsis-Induced Acute Lung Injury through Inhibiting NLRP3 Inflammasome-Dependent Pyroptosis in Mice Model.二氢杨梅素通过抑制 NLRP3 炎性小体依赖性细胞焦亡缓解脓毒症诱导的急性肺损伤。
Inflammation. 2019 Aug;42(4):1301-1310. doi: 10.1007/s10753-019-00990-7.
9
Dynamic molecular changes during the first week of human life follow a robust developmental trajectory.在人类生命的第一周，动态分子变化遵循着强大的发育轨迹。
Nat Commun. 2019 Mar 12;10(1):1092. doi: 10.1038/s41467-019-08794-x.
10
Murine astrocytes produce IL-24 and are susceptible to the immunosuppressive effects of this cytokine.鼠源星形胶质细胞产生白细胞介素-24 并易受该细胞因子免疫抑制作用的影响。
J Neuroinflammation. 2019 Mar 2;16(1):55. doi: 10.1186/s12974-019-1444-1.
Zotero 插件