Neonatal Group B Streptococcal Disease in Otherwise Healthy Infants: Failure of Specific Neonatal Immune Responses.
Neonatal Group B Streptococcal Disease in Otherwise Healthy Infants: Failure of Specific Neonatal Immune Responses.
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DOI：
10.3389/fimmu.2017.00215
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发表时间：
2017
影响因子：
7.3
通讯作者：
Fellay J
中科院分区：
文献类型：
--
作者：
Borghesi A;Stronati M;Fellay J
只有一小部分接触病原微生物的新生儿会出现明显的感染。早产儿和已知合并症婴儿的感染易感性可能有多因素来源，通常可归因于医源性因素、环境决定因素、潜在致病过程和可能的遗传易感性的同时发生。相反，在大多数情况下，健康的足月新生儿发生感染是无法解释的。微生物毒力因子和新生儿免疫系统的独特特征仅部分解释了新生儿对病原体免疫应答的个体间差异。我们认为，新生儿感染发生在其他健康的婴儿是由于对微生物的特异性保护性免疫的失败。为了解释足月儿和早产儿的感染，我们提出了以前提出的人类传染病遗传结构模型的扩展。然后，我们专注于B组链球菌（GBS）疾病，最具特色的新生儿感染，并概述了潜在的分子机制的选择性失败的免疫反应对GBS。鉴于最近发现的病原体特异性原发性免疫缺陷和抗细胞因子自身抗体在增加对特定感染的易感性中的作用，我们假设GBS疾病发生在其他健康婴儿中可能反映了婴儿罕见遗传缺陷或母亲传播的中和抗体引起的免疫缺陷。这些假设与现有的流行病学数据、临床和流行病学观察结果以及新生儿生理学和疾病的最新发展水平一致。现在应设计研究，全面寻找与严重新生儿感染易感性有关的遗传或免疫因素。
Only a small proportion of newborn infants exposed to a pathogenic microorganism develop overt infection. Susceptibility to infection in preterm infants and infants with known comorbidities has a likely multifactorial origin and can be often attributed to the concurrence of iatrogenic factors, environmental determinants, underlying pathogenic processes, and probably genetic predisposition. Conversely, infection occurring in otherwise healthy full-term newborn infants is unexplained in most cases. Microbial virulence factors and the unique characteristics of the neonatal immune system only partially account for the interindividual variability in the neonatal immune responses to pathogens. We here suggest that neonatal infection occurring in otherwise healthy infants is caused by a failure of the specific protective immunity to the microorganism. To explain infection in term and preterm infants, we propose an extension of the previously proposed model of the genetic architecture of infectious diseases in humans. We then focus on group B streptococcus (GBS) disease, the best characterized neonatal infection, and outline the potential molecular mechanisms underlying the selective failure of the immune responses against GBS. In light of the recent discoveries of pathogen-specific primary immunodeficiencies and of the role of anticytokine autoantibodies in increasing susceptibility to specific infections, we hypothesize that GBS disease occurring in otherwise healthy infants could reflect an immunodeficiency caused either by rare genetic defects in the infant or by transmitted maternal neutralizing antibodies. These hypotheses are consistent with available epidemiological data, with clinical and epidemiological observations, and with the state of the art of neonatal physiology and disease. Studies should now be designed to comprehensively search for genetic or immunological factors involved in susceptibility to severe neonatal infections.