Aberrant placental immune parameters in the feline immunodeficiency virus (FIV)-infected cat suggest virus-induced changes in T cell function.
Aberrant placental immune parameters in the feline immunodeficiency virus (FIV)-infected cat suggest virus-induced changes in T cell function.
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DOI：
10.1186/1743-422x-10-238
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发表时间：
2013-07-19
期刊：
影响因子：
4.8
通讯作者：
Coats KS
中科院分区：
文献类型：
--
作者：
Chumbley LB;Boudreaux CE;Coats KS
怀孕期间的免疫活动必须严格调节，以确保成功怀孕。这种调节包括抑制可能靶向半同种异体胎儿的炎症活动。T细胞是免疫抑制性的; Th 17细胞是促炎细胞。两种细胞群的精确平衡对于维持妊娠至关重要，而这种平衡的失调伴随着人类和小鼠的妊娠受损。已知FIV在感染猫中优先靶向Tcl 3。因此，可以假设FIV感染改变了胎盘Treg/Th 17细胞平衡，导致这些细胞的异常免疫调节剂表达和随后的妊娠干扰。从妊娠早期未感染和感染FIV的蜂王收集的整个胎盘组织的随机切片中纯化RNA，包括活胎和死胎的组织。进行了真实的时间qPCR以定量TcB（FoxP 3）和Th 17细胞（RORγ）的核内标志物; TcB（IL-10和TGF-β）、Th 17细胞（IL-2、IL-6和IL-17 α）和巨噬细胞（IL-1β）的细胞因子产物;以及FIV gag基因的表达。进行成对比较以评估细胞因子之间以及细胞因子与病毒之间的共表达模式。FoxP 3和RORγ在感染动物的胎盘中均减少。感染状态和胎儿存活率均不影响IL-1β的胎盘表达。然而，胎儿的非活力与所有其他细胞因子水平的降低有关。感染和胎儿不存活影响各种细胞因子对的共表达。未观察到对Treg或Th 17细胞的明显偏向。FIV感染与胎儿不存活相结合改变了T细胞细胞因子的表达模式。这些数据表明，功能改变的胎盘T细胞白细胞群可能发生在感染的女王，并可能有助于胎儿的非活力。
Immune activity during pregnancy must be tightly regulated to ensure successful pregnancy. This regulation includes the suppression of inflammatory activity that could target the semi-allogeneic fetus. Tregs are immunosuppressive; Th17 cells are pro-inflammatory. A precise balance in the two cell populations is critical to pregnancy maintenance, while dysregulation in this balance accompanies compromised pregnancy in humans and mice. FIV is known to target Tregs preferentially in the infected cat. Therefore, it may be hypothesized that FIV infection alters the placental Treg/Th17 cell balance resulting in aberrant immunomodulator expression by these cells and consequent pregnancy perturbation. RNA was purified from random sections of whole placental tissues collected from both uninfected and FIV-infected queens at early pregnancy, including tissues from viable and nonviable fetuses. Real time qPCR was performed to quantify expression of intranuclear markers of Tregs (FoxP3) and Th17 cells (RORγ); cytokine products of Tregs (IL-10 and TGF-β), Th17 cells (IL-2, IL-6, and IL-17a), and macrophages (IL-1β); and the FIV gag gene. Pairwise comparisons were made to evaluate coexpression patterns between the cytokines and between the cytokines and the virus. Both FoxP3 and RORγ were reduced in placentas of infected animals. Neither infection status nor fetal viability affected placental expression of IL-1β. However, fetal nonviability was associated with reduced levels of all other cytokines. Infection and fetal nonviability impacted coexpression of various cytokine pairs. No obvious bias toward Treg or Th17 cells was observed. FIV infection coupled with fetal nonviability alters expression patterns of T cell cytokines. These data suggest that functionally altered placental T cell leukocyte populations may occur in the infected queen and possibly contribute to fetal nonviability.