Paris-City University, Mére et Enfants en Milieu Tropical: pathogénes, systéme de santé et transition épidémiologique (MERIT), Institute of Research for Development (IRD), Paris, France.
Faculty of Sciences and Technology (FAST), University of Abomey-Calavi, Institute of Applied Biomedical Sciences (ISBA), Laboratory of Cell Biology and Physiology, Cotonou, Benin.
Front Immunol. 2024 Jul 12;15:1420554. doi: 10.3389/fimmu.2024.1420554. eCollection 2024.
Regulatory T cells (Treg) play a prominent role tolerating non-inherited maternal antigens and in regulating immune responses against pathogens at birth. This study investigates Treg immunity in newborns in West Africa, where sepsis remains a major public health problem. Treg phenotypes on neonates subgroups with early-onset sepsis (EOS), presumed sepsis, and healthy newborn with and without prenatal risk factors were evaluated. Treg phenotypes varied according to prenatal conditions, with increase in Treg frequency and Foxp3 expression in healthy newborns with prenatal risk factors compared to those with none risk. Compared to healthy newborns with prenatal risk factors, EOS neonates had a significantly reduced frequency of Treg and Foxp3 expression. In the Treg pool, higher frequency of activated Treg was observed in EOS neonates, suggesting an activation upstream of the sepsis onset. Their migration to the infection site may explain the reduced frequency of circulating Integrin α4β1 Treg suggestive of homing to the endothelial tissue. EOS neonates show increases expression of CTLA-4, PD-1 and CD39 on Treg, which negatively regulate the activation of effector T cells (Teff) corroborating by the lower frequency of Teff in EOS neonates. The higher frequency of CD39 Treg and the lower frequency of integrinα4β1 Treg in EOS non-survivor suggests that Treg exhaustement and endothelial homing are associated with outcome severity. Neonates developing EOS are born with an altered Treg phenotypic profile. Treg expression of CTLA-4, PD-1, CD39, and integrinα4β1 cell markers can be considered as early warning or diagnostic markers of EOS.
调节性 T 细胞（Treg）在容忍非遗传性母体抗原和调节出生时对病原体的免疫反应方面发挥着重要作用。本研究调查了西非新生儿的 Treg 免疫情况，在西非，败血症仍然是一个主要的公共卫生问题。评估了具有早发性败血症（EOS）、疑似败血症和健康新生儿的新生儿亚组的 Treg 表型，这些新生儿有无产前危险因素。Treg 表型根据产前情况而有所不同，与无风险因素的健康新生儿相比，有产前风险因素的健康新生儿 Treg 频率增加，Foxp3 表达增加。与有产前风险因素的健康新生儿相比，EOS 新生儿 Treg 的频率和 Foxp3 表达显著降低。在 Treg 群体中，EOS 新生儿中观察到活化的 Treg 频率更高，这表明在败血症发作之前存在 Treg 的激活。它们向感染部位的迁移可能解释了循环中 Integrinα4β1 Treg 频率降低，提示它们向内皮组织归巢。EOS 新生儿 Treg 上 CTLA-4、PD-1 和 CD39 的表达增加，这些分子负调节效应 T 细胞（Teff）的激活，EOS 新生儿 Teff 频率较低佐证了这一点。EOS 非幸存者中 CD39 Treg 频率较高和 Integrinα4β1 Treg 频率较低表明 Treg 耗竭和内皮归巢与结局严重程度相关。发生 EOS 的新生儿出生时具有改变的 Treg 表型特征。CTLA-4、PD-1、CD39 和 Integrinα4β1 细胞标志物的 Treg 表达可以被认为是 EOS 的早期预警或诊断标志物。
