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Maternal vaccination against group B Streptococcus glyceraldehyde-3-phosphate dehydrogenase leads to gut dysbiosis in the offspring
Brain, Behavior, and Immunity ( IF 8.8 ) Pub Date : 2022-04-12 , DOI: 10.1016/j.bbi.2022.04.004
Elva Bonifácio Andrade 1 , Inês Lorga 1 , Susana Roque 2 , Rafaela Geraldo 3 , Pedro Mesquita 3 , Rogério Castro 2 , Luísa Simões-Costa 4 , Madalena Costa 5 , Augusto Faustino 3 , Adília Ribeiro 1 , Margarida Correia-Neves 2 , Patrick Trieu-Cuot 6 , Paula Ferreira 1
Affiliation  

Group B Streptococcus (GBS) remains a major neonatal life-threatening pathogen. We initially identified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a promising vaccine candidate against GBS. Since GAPDH is highly conserved, we investigate whether GBS GAPDH maternal vaccination interferes with the intestinal colonization of the offspring and the development of its mucosal immune system and central nervous system. An altered gut microbiome with increased Proteobacteria is observed in pups born from vaccinated dams during early life. These pups present decreased relative expression of IL-1β, IL-17A, RegIIIγ and MUC2 in the distal colon. They also display increased CD11b, F4/80 and MHC class II expression on microglia in early life and marked reduction of Ly6C+ cells and neutrophils. Importantly, male mice born from vaccinated mothers present behavioral abnormalities during adulthood, including decreased exploratory behavior, a subtle anxious-like phenotype and global alterations in spatial learning and memory strategies, and higher sensitivity to a stressful stimulus. Our study highlights the danger of using ubiquitous antigens in maternal human vaccines against neonatal pathogens.



中文翻译:

母体接种 B 群链球菌 3-磷酸甘油醛脱氢酶会导致后代肠道生态失调

B 组链球菌(GBS) 仍然是威胁新生儿生命的主要病原体。我们最初将 3-磷酸甘油醛脱氢酶 (GAPDH) 确定为一种有希望的针对 GBS 的候选疫苗。由于 GAPDH 高度保守,我们研究了 GBS GAPDH 母体疫苗接种是否会干扰后代的肠道定植及其粘膜免疫系统和中枢神经系统的发育。在早期接种疫苗的水坝出生的幼崽中观察到改变的肠道微生物群和增加的变形菌。这些幼崽在远端结肠中表现出 IL-1β、IL-17A、RegIIIγ 和 MUC2 的相对表达降低。它们还显示早期小胶质细胞上 CD11b、F4/80 和 MHC II 类表达增加,Ly6C +显着减少细胞和中性粒细胞。重要的是,接种疫苗的母亲所生的雄性小鼠在成年期表现出行为异常,包括探索行为减少、微妙的焦虑样表型和空间学习和记忆策略的整体改变,以及对压力刺激的更高敏感性。我们的研究强调了在针对新生儿病原体的母体人类疫苗中使用普遍存在的抗原的危险。

更新日期:2022-04-12
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