Price Aryn A, Tedesco Dana, Prasad Mona R, Workowski Kimberly A, Walker Christopher M, Suthar Mehul S, Honegger Jonathan R, Grakoui Arash
Emory Vaccine Center, Division of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30329; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329;
Department of Obstetrics and Gynecology, The Ohio State University School of Medicine, Columbus, OH 43205;
Proc Natl Acad Sci U S A. 2016 Sep 20;113(38):10678-83. doi: 10.1073/pnas.1602319113. Epub 2016 Sep 6.
Maternal innate and adaptive immune responses are modulated during pregnancy to concurrently defend against infection and tolerate the semiallogeneic fetus. The restoration of these systems after childbirth is poorly understood. We reasoned that enhanced innate immune activation may extend beyond gestation while adaptive immunity recovers. To test this hypothesis, the transcriptional profiles of total peripheral blood mononuclear cells following delivery in healthy women were compared with those of nonpregnant control subjects. Interestingly, interferon-stimulated genes (ISGs) encoding proteins such as IFIT1, IFIT2, and IFIT3, as well as signaling proteins such as STAT1, STAT2, and MAVS, were enriched postpartum. Antiviral genes were primarily expressed in CD14(+) cells and could be stratified according to genetic variation at the interferon-λ3 gene (IFNL3, also named IL28B) SNP rs12979860. Antiviral gene expression was sustained beyond 6 mo following delivery in mothers with a CT or TT genotype, but resembled baseline nonpregnant control levels following delivery in mothers with a CC genotype. CT and TT IFNL3 genotypes have been associated with persistent elevated ISG expression in individuals chronically infected with hepatitis C virus. Together, these data suggest that postpartum, the normalization of the physiological rheostat controlling IFN signaling depends on IFNL3 genotype.
孕期母体的先天性和适应性免疫反应受到调节，以同时抵御感染并耐受半同种异体胎儿。产后这些系统的恢复情况尚不清楚。我们推测，在适应性免疫恢复的同时，先天性免疫激活增强可能会持续到产后。为了验证这一假设，我们将健康女性分娩后外周血单个核细胞的转录谱与未怀孕对照受试者的转录谱进行了比较。有趣的是，产后编码IFIT1、IFIT2和IFIT3等蛋白质的干扰素刺激基因（ISG）以及STAT1、STAT2和MAVS等信号蛋白有所富集。抗病毒基因主要在CD14(+)细胞中表达，并且可以根据干扰素-λ3基因（IFNL3，也称为IL28B）SNP rs12979860处的基因变异进行分层。在基因型为CT或TT的母亲中，抗病毒基因表达在分娩后6个月以上仍持续存在，但在基因型为CC的母亲中，分娩后其抗病毒基因表达水平类似于未怀孕对照受试者的基线水平。CT和TT IFNL3基因型与慢性丙型肝炎病毒感染者中ISG表达持续升高有关。这些数据共同表明，产后控制IFN信号传导的生理调节机制的正常化取决于IFNL3基因型。
