感染易感性儿童对肺炎链球菌的辅助性T细胞17反应降低，可通过添加天然细胞因子来挽救。
Reduced T-Helper 17 Responses to Streptococcus pneumoniae in Infection-Prone Children Can Be Rescued by Addition of Innate Cytokines.
作者信息
Basha Saleem, Kaur Ravinder, Mosmann Tim R, Pichichero Michael E
机构信息
Center for Infectious Diseases and Immunology, Rochester General Hospital Research Institute and.
Human Immunology Center, University of Rochester Medical Center, New York.
出版信息
J Infect Dis. 2017 Apr 15;215(8):1321-1330. doi: 10.1093/infdis/jix090.
Abstract
BACKGROUND
T-helper (Th) 17 cells are important in the control of Streptococcus pneumoniae. We sought to understand the mechanism of failure of Th17 immunity resulting in S. pneumoniae infections in children <2 years old.
METHODS
Peripheral blood mononuclear cells (PBMCs) from infection-prone (IP) and non-IP (NIP) children 9-18 months old were examined for their responses to heat-killed S. Pneumoniae, using flow cytometry, reverse-transcription polymerase chain reaction, and enzyme-linked immunoassay. We measured cytokine production, proliferation, and differentiation of Th17 cells and the expression of transcription factors in response to S. pneumoniae.
RESULTS
PBMCs of IP children stimulated with heat-killed S. pneumoniae had significantly reduced percentages of CD4+ Th1 (interleukin2, tumor necrosis factor α) and Th17 (interleukin 17A) cells compared with NIP children. Addition of exogenous Th17-promoting cytokines (interleukin 6, 1β, and 23 and transforming growth factor β) restored CD4+ Th17 cell function in cells from IP children to levels measured in NIP children.
CONCLUSIONS
Reduced Th17 responses to S. pneumoniae in PBMCs of IP children can be rescued by addition of Th17-promoting cytokines.
摘要
背景
辅助性T细胞17（Th17）在控制肺炎链球菌感染中起重要作用。我们试图了解2岁以下儿童Th17免疫功能衰竭导致肺炎链球菌感染的机制。
方法
采用流式细胞术、逆转录聚合酶链反应和酶联免疫吸附测定法，检测9 - 18个月大的易感染（IP）儿童和非易感染（NIP）儿童外周血单个核细胞（PBMC）对热灭活肺炎链球菌的反应。我们测量了Th17细胞的细胞因子产生、增殖和分化以及对肺炎链球菌反应时转录因子的表达。
结果
与NIP儿童相比，热灭活肺炎链球菌刺激的IP儿童PBMC中，CD4 + Th1（白细胞介素2、肿瘤坏死因子α）和Th17（白细胞介素17A）细胞的百分比显著降低。添加外源性Th17促进细胞因子（白细胞介素6、1β、23和转化生长因子β）可将IP儿童细胞中的CD4 + Th17细胞功能恢复到NIP儿童中测得的水平。
结论
添加Th17促进细胞因子可挽救IP儿童PBMC中对肺炎链球菌反应降低的Th17反应。
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