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新生儿卡介苗接种可降低随机对照试验中婴儿对异源病原体的干扰素-γ反应性。

Neonatal BCG Vaccination Reduces Interferon-γ Responsiveness to Heterologous Pathogens in Infants From a Randomized Controlled Trial.

机构信息

Infectious Diseases and Microbiology Group, Murdoch Children's Research Institute, Royal Children's Hospital Melbourne, Parkville, Australia.

Department of Paediatrics, The University of Melbourne, Parkville, Australia.

出版信息

J Infect Dis. 2020 Jun 11;221(12):1999-2009. doi: 10.1093/infdis/jiaa030.

DOI:10.1093/infdis/jiaa030
PMID:31990350
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7289544/
Abstract

BACKGROUND

BCG vaccination has beneficial nonspecific (heterologous) effects that protect against nonmycobacterial infections. We have previously reported that BCG vaccination at birth alters in vitro cytokine responses to heterologous stimulants in the neonatal period. This study investigated heterologous responses in 167 infants in the same trial 7 months after randomization.

METHODS

A whole-blood assay was used to interrogate in vitro cytokine responses to heterologous stimulants (killed pathogens) and Toll-like receptor (TLR) ligands.

RESULTS

Compared to BCG-naive infants, BCG-vaccinated infants had increased production of interferon gamma (IFN-γ) and monokine induced by gamma interferon (MIG) (CXCL9) in response to mycobacterial stimulation and decreased production of IFN-γ in response to heterologous stimulation and TLR ligands. Reduced IFN-γ responses were attributable to a decrease in the proportion of infants who mounted a detectable IFN-γ response. BCG-vaccinated infants also had increased production of MIG (CXCL9) and interleukin-8 (IL-8), and decreased production of IL-10, macrophage inflammatory protein-1α (MIP-1α), and MIP-1β, the pattern of which varied by stimulant. IL-1Ra responses following TLR1/2 (Pam3CYSK4) stimulation were increased in BCG-vaccinated infants. Both sex and maternal BCG vaccination status influenced the effect of neonatal BCG vaccination.

CONCLUSIONS

BCG vaccination leads to changes in IFN-γ responsiveness to heterologous stimulation. BCG-induced changes in other cytokine responses to heterologous stimulation vary by pathogen.

摘要

背景

卡介苗（BCG）接种具有有益的非特异性（异源）效应，可以预防非分枝杆菌感染。我们之前报道过，出生时接种 BCG 会改变新生儿期对异源刺激物的体外细胞因子反应。本研究在同一试验中，于随机分组后 7 个月，调查了 167 名婴儿的异源反应。

方法

使用全血检测法，检测异源刺激物（已杀灭的病原体）和 Toll 样受体（TLR）配体刺激下体外细胞因子反应。

结果

与未接种 BCG 的婴儿相比，接种 BCG 的婴儿对分枝杆菌刺激的干扰素γ（IFN-γ）和γ干扰素诱导的单核细胞趋化蛋白 1（MIG，CXCL9）的产生增加，而对异源刺激和 TLR 配体的 IFN-γ产生减少。IFN-γ 反应减少归因于能产生可检测 IFN-γ 反应的婴儿比例降低。接种 BCG 的婴儿还增加了 MIG（CXCL9）和白细胞介素-8（IL-8）的产生，减少了 IL-10、巨噬细胞炎症蛋白-1α（MIP-1α）和 MIP-1β的产生，其模式因刺激物而异。TLR1/2（Pam3CYSK4）刺激后，IL-1Ra 反应在接种 BCG 的婴儿中增加。婴儿的性别和母亲的 BCG 接种状况均影响新生儿 BCG 接种的效果。

结论

BCG 接种导致对异源刺激的 IFN-γ 反应性发生变化。BCG 诱导的对异源刺激的其他细胞因子反应变化因病原体而异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2725/7289544/3eb3c63e8df4/jiaa030f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2725/7289544/0fa85c6511de/jiaa030f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2725/7289544/4b72bab3833a/jiaa030f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2725/7289544/52c8589f6e36/jiaa030f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2725/7289544/3eb3c63e8df4/jiaa030f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2725/7289544/0fa85c6511de/jiaa030f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2725/7289544/4b72bab3833a/jiaa030f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2725/7289544/52c8589f6e36/jiaa030f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2725/7289544/3eb3c63e8df4/jiaa030f0004.jpg

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