Key Points Perforin-2 plays a protective role in infections of the placenta. Both maternal- and fetal-encoded perforin-2 contribute to protection. Perforin-2 is differentially expressed in placental macrophages during infection. Placental immune responses are highly regulated to strike a balance between protection and tolerance. For relatively mild infections, protection encompasses both the mother and fetus; however, during worsening conditions, protection becomes exclusively reserved for the mother. Previously, we and others have shown that the host factor perforin-2 plays a central role in protecting mice and cells against infection. In this study, we analyzed perforin-2 activity in the mouse placenta to determine whether perforin-2 plays a similarly protective role. We show that perforin-2 is critical for inhibiting Listeria monocytogenes colonization of the placenta and fetus and that this protection is due to both maternal and fetal-encoded perforin-2. Perforin-2 mRNA is readily detectable in individual immune cells of the decidua, and these levels are further enhanced specifically in decidual macrophages during high-dose infections that result in fetal expulsion. Unexpectedly, inductive perforin-2 expression in decidual macrophages did not occur during milder infections in which fetal viability remained intact. This pattern of expression significantly differed from that observed in splenic macrophages in which inductive perforin-2 expression was observed in both high and mild infection conditions. In the placenta, inductive perforin-2 expression in decidual macrophages was coincident with their polarization from a CD206+ MHC class IIlo to CD206− MHC class IIhi phenotype that normally occurs in the placenta during high-burden infections. Our results suggest that perforin-2 is part of a host response that is protective either for both the mother and fetus in milder infections or exclusively for the mother during high-dose infections.

中文翻译：

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母体和胎儿编码的 Perforin-2 限制血源性病原体对胎盘的感染

要点 Perforin-2 在胎盘感染中起保护作用。母体和胎儿编码的 perforin-2 都有助于保护。Perforin-2 在感染期间在胎盘巨噬细胞中差异表达。胎盘免疫反应受到高度调节，以在保护和耐受之间取得平衡。对于相对轻微的感染，保护包括母亲和胎儿；然而，在病情恶化的情况下，保护只留给母亲。此前，我们和其他人已经证明宿主因子 perforin-2 在保护小鼠和细胞免受感染方面起着核心作用。在这项研究中，我们分析了小鼠胎盘中 perforin-2 的活性，以确定 perforin-2 是否起到类似的保护作用。我们表明 perforin-2 对抑制单核细胞增生李斯特菌在胎盘和胎儿的定植至关重要，这种保护作用是由于母体和胎儿编码的 perforin-2。Perforin-2 mRNA 在蜕膜的单个免疫细胞中很容易检测到，并且在导致胎儿排出的高剂量感染期间，这些水平在蜕膜巨噬细胞中进一步增强。出乎意料的是，在胎儿活力保持完整的轻度感染期间，蜕膜巨噬细胞中的诱导性 perforin-2 表达并未发生。这种表达模式与在脾脏巨噬细胞中观察到的表达模式显着不同，后者在高感染和轻度感染条件下均观察到诱导性 perforin-2 表达。在胎盘中，蜕膜巨噬细胞中的诱导性穿孔素 2 表达与其从 CD206+ MHC IIlo 类到 CD206- MHC IIhi 类表型的极化相一致，这通常在高负荷感染期间发生在胎盘中。我们的结果表明，perforin-2 是宿主反应的一部分，在轻度感染中对母体和胎儿都有保护作用，或者在高剂量感染时仅对母体具有保护作用。