Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Detroit, MI;
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI.
J Immunol. 2022 Apr 15;208(8):1857-1872. doi: 10.4049/jimmunol.2101123. Epub 2022 Apr 4.
Pregnant women are at increased risk of adverse outcomes, including preeclampsia and preterm birth, that may result from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Pregnancy imprints specific maternal immune responses that can modulate host susceptibility to microbial infection; therefore, recent studies have focused on the humoral response against SARS-CoV-2 in pregnant women. However, the pregnancy-specific cellular immune responses triggered by SARS-CoV-2 infection are poorly understood. In this study, we undertook an extensive in vitro investigation to determine the cellular immune responses to SARS-CoV-2 particles and proteins/peptides in pregnant women. First, we show that SARS-CoV-2 particles do not alter the pregnancy-specific oxidative burst of neutrophils and monocytes. Yet, SARS-CoV-2 particles/proteins shift monocyte activation from the classical to intermediate states in pregnant, but not in nonpregnant, women. Furthermore, SARS-CoV-2 proteins, but not particles or peptide pools, mildly enhance T cell activation during pregnancy. As expected, B cell phenotypes are heavily modulated by SARS-CoV-2 particles in all women; yet, pregnancy itself further modified such responses in these adaptive immune cells. Lastly, we report that pregnancy itself governs cytokine responses in the maternal circulation, of which IFN-β and IL-8 were diminished upon SARS-CoV-2 challenge. Collectively, these findings highlight the differential in vitro responses to SARS-CoV-2 in pregnant and nonpregnant women and shed light on the immune mechanisms implicated in coronavirus disease 2019 during pregnancy.
孕妇发生不良结局的风险增加，包括子痫前期和早产，这可能是由严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染引起的。妊娠会引起特定的母体免疫反应，从而调节宿主对微生物感染的易感性；因此，最近的研究集中在针对 SARS-CoV-2 的孕妇体液免疫反应上。然而，SARS-CoV-2 感染引发的妊娠特异性细胞免疫反应还知之甚少。在这项研究中，我们进行了广泛的体外研究，以确定 SARS-CoV-2 颗粒和蛋白质/肽在孕妇中的细胞免疫反应。首先，我们表明 SARS-CoV-2 颗粒不会改变中性粒细胞和单核细胞的妊娠特异性氧化爆发。然而，SARS-CoV-2 颗粒/蛋白质会使单核细胞的激活从经典状态转变为妊娠女性的中间状态，但不会转变为非妊娠女性的中间状态。此外，SARS-CoV-2 蛋白会轻度增强 T 细胞在妊娠期间的激活，而不是颗粒或肽库。正如预期的那样，SARS-CoV-2 颗粒在所有女性中都严重调节 B 细胞表型；然而，妊娠本身进一步改变了这些适应性免疫细胞的这些反应。最后，我们报告妊娠本身控制母体循环中的细胞因子反应，其中 IFN-β 和 IL-8 在 SARS-CoV-2 攻击后减少。总之，这些发现强调了 SARS-CoV-2 在孕妇和非孕妇中的体外反应存在差异，并阐明了在 COVID-19 期间与妊娠相关的冠状病毒病 2019 免疫机制。
