Francis J P, Richmond P C, Strickland D, Prescott S L, Pomat W S, Michael A, Nadal-Sims M A, Edwards-Devitt C J, Holt P G, Lehmann D, van den Biggelaar A H J
Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea.
School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.
Clin Exp Immunol. 2017 Mar;187(3):408-417. doi: 10.1111/cei.12902. Epub 2016 Dec 18.
In areas where Streptococcus pneumoniae is highly endemic, infants experience very early pneumococcal colonization of the upper respiratory tract, with carriage often persisting into adulthood. We aimed to explore whether newborns in high-risk areas have pre-existing pneumococcal-specific cellular immune responses that may affect early pneumococcal acquisition. Cord blood mononuclear cells (CBMC) of 84 Papua New Guinean (PNG; high endemic) and 33 Australian (AUS; low endemic) newborns were stimulated in vitro with detoxified pneumolysin (dPly) or pneumococcal surface protein A (PspA; families 1 and 2) and compared for cytokine responses. Within the PNG cohort, associations between CBMC dPly and PspA-induced responses and pneumococcal colonization within the first month of life were studied. Significantly higher PspA-specific interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-5, IL-6, IL-10 and IL-13 responses, and lower dPly-IL-6 responses were produced in CBMC cultures of PNG compared to AUS newborns. Higher CBMC PspA-IL-5 and PspA-IL-13 responses correlated with a higher proportion of cord CD4 T cells, and higher dPly-IL-6 responses with a higher frequency of cord antigen-presenting cells. In the PNG cohort, higher PspA-specific IL-5 and IL-6 CBMC responses were associated independently and significantly with increased risk of earlier pneumococcal colonization, while a significant protective effect was found for higher PspA-IL-10 CBMC responses. Pneumococcus-specific cellular immune responses differ between children born in pneumococcal high versus low endemic settings, which may contribute to the higher risk of infants in high endemic settings for early pneumococcal colonization, and hence disease.
在肺炎链球菌高度流行的地区，婴儿的上呼吸道会很早出现肺炎链球菌定植，且这种携带状态常常会持续到成年期。我们旨在探究高风险地区的新生儿是否存在预先存在的肺炎链球菌特异性细胞免疫反应，这种反应可能会影响肺炎链球菌的早期感染。对84名巴布亚新几内亚（PNG；高流行地区）和33名澳大利亚（AUS；低流行地区）新生儿的脐带血单个核细胞（CBMC）进行体外刺激，分别用解毒肺炎溶血素（dPly）或肺炎球菌表面蛋白A（PspA；1型和2型家族）刺激，然后比较细胞因子反应。在PNG队列中，研究了CBMC的dPly和PspA诱导反应与出生后第一个月内肺炎链球菌定植之间的关联。与AUS新生儿相比，PNG新生儿的CBMC培养物中产生的PspA特异性干扰素（IFN）-γ、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-5、IL-6、IL-10和IL-13反应显著更高，而dPly-IL-6反应更低。更高的CBMC PspA-IL-5和PspA-IL-13反应与脐带血CD4 T细胞比例较高相关，更高的dPly-IL-6反应与脐带血抗原呈递细胞频率较高相关。在PNG队列中，更高的PspA特异性IL-5和IL-6 CBMC反应与早期肺炎链球菌定植风险增加独立且显著相关，而更高的PspA-IL-10 CBMC反应则具有显著的保护作用。肺炎链球菌高流行地区和低流行地区出生的儿童之间，肺炎链球菌特异性细胞免疫反应存在差异，这可能导致高流行地区婴儿早期肺炎链球菌定植及患病风险更高。
