Clark Dayna R, Chaturvedi Vandana, Kinder Jeremy M, Jiang Tony T, Xin Lijun, Ertelt James M, Way Sing Sing
Cell Mol Immunol. 2014 Nov;11(6):595-605. doi: 10.1038/cmi.2014.84. Epub 2014 Sep 22.
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.
单核细胞增生李斯特菌(Lm)是一种胞内细菌,在孕期易引发母体全身性感染,并对发育中的胎儿造成不良后果。鉴于产前Lm感染相关的高死亡率,迫切需要在孕期这个极其脆弱的时期增强保护性免疫的策略。在此,我们评估了孕前接种减毒Lm对后续产前强毒Lm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感染的保护作用显著减弱,因为尽管病原体特异性CD8(+) T细胞的数量和功能得以保留,但从母体组织中回收的细菌明显更多。更重要的是,孕前免疫不能预防子宫内感染或胎儿死亡,因为孕前接种减毒Lm的小鼠和未免疫的妊娠对照小鼠在孕期感染Lm后,各自都出现了几乎完全的胎儿吸收和从单个胚胎中回收病原体的情况。值得注意的是,在同基因妊娠期间,同种异体妊娠中孕前免疫对产前Lm感染缺乏保护的情况得以恢复。因此,母胎抗原不一致决定了孕前接种疫苗对产前Lm感染后胎儿并发症无效,尽管病原体特异性CD8(+) T细胞的数量和功能得以保留。