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Nucleic acid cytokine responses in obese children and infants of obese mothers

机译：肥胖儿童和肥胖母亲婴儿的核酸细胞因子反应

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Almost a third of Irish children are now overweight and the country ranks 58th out of 200 countries for its proportion of overweight youths. With the rising obesity epidemic, and the impaired immune responses of this population, it is vital to understand the effects that obesity has on the immune system and to design future therapeutics, adjuvants and vaccines with overweight and obese populations in mind. Many current vaccines use adjuvants that have been found to be less effective at stimulating the immune response in children compared with adults and there is now substantial effort to design paediatric-focused adjuvants. Additionally, vaccine responses have been shown to be less effective in obese populations indicating that this is a particularly vulnerable population. We have recently identified cytosolic nucleic acids (CNAs), as novel candidate adjuvants for childhood vaccines. Here we investigated whether immune responses to these candidate adjuvants were adversely affected in infants born to overweight or obese mothers, and in overweight and obese children. Type I Interferon (IFN) and proinflammatory cytokines such as Tumor Necrosis Factor alpha (TNF alpha) are vital for driving innate and adaptive immune responses. We found that childhood obesity conferred no significant adverse effect on CNA-induced Type I IFN responses when compared with lean children. Similarly, Type I IFN responses were intact in the cord blood of babies delivered from overweight and obese mothers, when compared with lean mothers. There was also no significant impact of obesity on CNA-induced TNF alpha responses in children or from cord blood of infants born to overweight/obese mothers. In all cases, there was a tendency towards decreased production of innate cytokine Type I Interferon and TNF alpha, however there was no significant negative correlation. Interestingly, high maternal BMI showed weak and moderate positive correlation with IL-12p70 and IFN gamma, respectively, in response to CNA stimulation. This study demonstrates that future adjuvants can be tailored for these populations through the use of activators of CNA sensors.
机译：现在，近三分之一的儿童现在超重，国家在200个国家中排名第58人，以其超重青年比例。随着肥胖流行的上升和这种人群的免疫反应受损，了解肥胖症对免疫系统的影响至关重要，并以超重和肥胖的人群设计未来的治疗剂，佐剂和疫苗。许多目前的疫苗使用已被发现的佐剂在刺激儿童的免疫应答时，与成人相比，现在有实质性努力设计聚焦辅助的佐剂。此外，已显示疫苗反应在肥胖群体中表明这是一个特别脆弱的人群。我们最近鉴定了细胞溶核酸（CNA），作为儿童疫苗的新候选辅助佐剂。在这里，我们调查了对这些候选辅助剂的免疫反应是否因超重或肥胖母亲的婴儿产生不利影响，以及超重和肥胖的儿童。 I型干扰素（IFN）和促炎细胞因子，例如肿瘤坏死因子α（TNF alpha）对于驱动先天和适应性免疫反应至关重要。与精益儿童相比，我们发现儿童肥胖赋予CNA诱导的I IFN反应没有显着的不良反应。同样，与超重和肥胖母亲的婴儿脐带血中，患有IFN反应的I型完整，与瘦母亲相比。肥胖症对儿童的CNA诱导的TNFα反应也没有显着影响，或者从出生于超重/肥胖母亲的婴儿的脐带血。在所有情况下，患有先天细胞因子型Interferon和TNF alpha的产生的趋势趋势，但没有显着的负相关性。有趣的是，高母体BMI响应CNA刺激，分别与IL-12P70和IFNγ的弱和中等正相关。本研究表明，通过使用CNA传感器的活化剂，可以为这些群体量身定制未来的佐剂。

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