Maternal Antibiotic Treatment Impacts Development of the Neonatal Intestinal Microbiome and Antiviral Immunity
Maternal Antibiotic Treatment Impacts Development of the Neonatal Intestinal Microbiome and Antiviral Immunity
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DOI：
10.4049/jimmunol.1502322
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发表时间：
2016-05-01
影响因子：
4.4
通讯作者：
Lamouse-Smith, Esi S. N.
中科院分区：
文献类型：
--
作者：
Gonzalez-Perez, Gabriela;Hicks, Allison L.;Lamouse-Smith, Esi S. N.
婴儿胃肠道(GIT)的微生物定植始于出生，由母亲的微生物区系塑造，并因抗生素治疗而深刻改变。母亲在怀孕期间接受抗生素治疗会影响其婴儿胃肠道微生物区系的定植。GIT微生物区系在调节婴儿期针对系统性病毒感染的适应性免疫功能中的作用尚不清楚。我们使用围产期抗生素暴露的小鼠模型来检测GIT微生物失调对婴儿CD8(+)T细胞介导的抗病毒免疫的影响。孕期和哺乳期的母体抗生素治疗/治疗(MAT)导致母亲和婴儿胃肠道微生物区系的组成发生了深刻的变化。链球菌属垫子母亲的胃肠道微生物区系占主导地位，而垫子婴儿的胃肠道微生物区系以粪肠球菌为主。随后，MAT幼鼠在感染牛痘病毒后表现出死亡增加和加速的现象。在亚致死性感染的MAT幼鼠中，产生银特异性干扰素-γ的CD8(+)T细胞减少。来自未感染幼鼠的MAT CD8(+)T细胞在体外激活后，维持干扰素-γ产生的能力也降低。此外，我们还确定，如果对照组幼鼠出生在使用更严格卫生标准的动物设施中，它们更容易受到感染。这些数据表明，婴儿时期GIT微生物区系的不受干扰的定植和发展对于促进强大的适应性抗病毒免疫反应是必要的。
Microbial colonization of the infant gastrointestinal tract (GIT) begins at birth, is shaped by the maternal microbiota, and is profoundly altered by antibiotic treatment. Antibiotic treatment of mothers during pregnancy influences colonization of the GIT microbiota of their infants. The role of the GIT microbiota in regulating adaptive immune function against systemic viral infections during infancy remains undefined. We used a mouse model of perinatal antibiotic exposure to examine the effect of GIT microbial dysbiosis on infant CD8(+) T cell-mediated antiviral immunity. Maternal antibiotic treatment/treated (MAT) during pregnancy and lactation resulted in profound alterations in the composition of the GIT microbiota in mothers and infants. Streptococcus spp. dominated the GIT microbiota of MAT mothers, whereas Enterococcus faecalis predominated within the MAT infant GIT. MAT infant mice subsequently exhibited increased and accelerated mortality following vaccinia virus infection. Ag-specific IFN-gamma-producing CD8(+) T cells were reduced in sublethally infected MAT infant mice. MAT CD8(+) T cells from uninfected infant mice also demonstrated a reduced capacity to sustain IFN-gamma production following in vitro activation. We additionally determined that control infant mice became more susceptible to infection if they were born in an animal facility using stricter standards of hygiene. These data indicate that undisturbed colonization and progression of the GIT microbiota during infancy are necessary to promote robust adaptive antiviral immune responses.