Perinatal Listeria monocytogenes susceptibility despite preconceptual priming and maintenance of pathogen-specific CD8+ T cells during pregnancy
Perinatal Listeria monocytogenes susceptibility despite preconceptual priming and maintenance of pathogen-specific CD8+ T cells during pregnancy
复制标题
DOI：
10.1038/cmi.2014.84
复制
发表时间：
2014-11-01
影响因子：
24.1
通讯作者：
Way, Sing Sing
中科院分区：
文献类型：
--
作者：
Clark, Dayna R.;Chaturvedi, Vandana;Way, Sing Sing
单核细胞增生李斯特氏菌 (Lm) 是一种细胞内细菌，具有独特的在妊娠期间引起全身性母体感染的倾向，并对发育中的胎儿造成病态后果。鉴于与产前 Lm 感染相关的高死亡率，迫切需要在极其脆弱的妊娠期增强保护性免疫力的策略。在此，评估了怀孕前给予减毒Lm所赋予的针对随后的有毒Lm产前感染的保护作用。我们发现，在同种异体妊娠期间，非妊娠小鼠对继发性 Lm 感染的保护作用急剧减弱，因为尽管病原体特异性 CD8(+) T 细胞在数量和功能上得到了保留，但从母体组织中回收了明显更多的细菌。更重要的是，孕前启动并不能防止子宫内侵入或胎儿流失，因为在怀孕前接种减毒Lm的小鼠和幼稚怀孕对照组在怀孕期间感染Lm后均表现出接近完全的胎儿吸收和病原体从个体受孕中恢复。值得注意的是，异基因妊娠中孕前启动对产前 Lm 感染缺乏保护的情况在同基因妊娠期间得到了恢复。因此，母胎抗原不一致决定了孕前疫苗接种对产前Lm感染后胎儿并发症的无效性，尽管病原体特异性CD8(+) T细胞的数量和功能得以保留。
Listeria monocytogenes (Lm) is an intracellular bacterium with unique predisposition for systemic maternal infection during pregnancy and morbid consequences for the developing fetus. Given the high mortality associated with prenatal Lm infection, strategies for augmenting protective immunity during the exceedingly vulnerable period of pregnancy are urgently needed. Herein, protection conferred by attenuated Lm administered before pregnancy against subsequent virulent Lm prenatal infection was evaluated. We show that protection against secondary Lm infection in non-pregnant mice is sharply moderated during allogeneic pregnancy because significantly more bacteria are recovered from maternal tissues, despite the numerical and functional preservation of pathogen-specific CD8(+) T cells. More importantly, preconceptual priming does not protect against in utero invasion or fetal wastage because mice inoculated with attenuated Lm prior to pregnancy and naive pregnant controls each showed near complete fetal resorption and pathogen recovery from individual concepti after Lm infection during pregnancy. Remarkably, the lack of protection against prenatal Lm infection with preconceptual priming in allogeneic pregnancy is restored during syngeneic pregnancy. Thus, maternal-fetal antigen discordance dictates the ineffectiveness of preconceptual vaccination against fetal complications after prenatal Lm infection, despite the numerical and functional preservation of pathogen-specific CD8(+) T cells.