Department of Biological Sciences, Mississippi State University, Mississippi State, MS 39762, USA.
Virol J. 2011 Jul 5;8:336. doi: 10.1186/1743-422X-8-336.
FIV infection frequently compromises pregnancy under experimental conditions and is accompanied by aberrant expression of some placental cytokines. Trophoblasts produce numerous immunomodulators that play a role in placental development and pregnancy maintenance. We hypothesized that FIV infection may cause dysregulation of trophoblast immunomodulator expression, and aberrant expression of these molecules may potentiate inflammation and compromise pregnancy. The purpose of this project was to evaluate the expression of representative pro-(TNF-α, IFN-γ, IL-1β, IL-2, IL-6, IL-12p35, IL-12p40, IL-18, and GM-CSF) and anti-inflammatory cytokines (IL-4, IL-5, and IL-10); CD134, a secondary co-stimulatory molecule expressed on activated T cells (FIV primary receptor); the chemokine receptor CXCR4 (FIV co-receptor); SDF-1α, the chemokine ligand to CXCR4; and FIV gag in trophoblasts from early-and late-term pregnancy.
We used an anti-cytokeratin antibody in immunohistochemistry to identify trophoblasts selectively, collected these cells using laser capture microdissection, and extracted total RNA from the captured cell populations. Real time, reverse transcription-PCR was used to quantify gene expression.
We detected IL-4, IL-5, IL-6, IL-1β, IL-12p35, IL-12p40, and CXCR4 in trophoblasts from early-and late-term pregnancy. Expression of cytokines increased from early to late pregnancy in normal tissues. A clear, pro-inflammatory microenvironment was not evident in trophoblasts from FIV-infected queens at either stage of pregnancy. Reproductive failure was accompanied by down-regulation of both pro-and anti-inflammatory cytokines. CD134 was not detected in trophoblasts, and FIV gag was detected in only one of ten trophoblast specimens collected from FIV-infected queens.
Feline trophoblasts express an array of pro-and anti-inflammatory immunomodulators whose expression increases from early to late pregnancy in normal tissues. Non-viable pregnancies were associated with decreased expression of immunomodulators which regulate trophoblast invasion in other species. The detection of FIV RNA in trophoblasts was rare, suggesting that the high rate of reproductive failure in FIV-infected queens was not a direct result of viral replication in trophoblasts. The influence of placental immune cells on trophoblast function and pregnancy maintenance in the FIV-infected cat requires additional study.
在实验条件下，FIV 感染常导致妊娠失败，并伴有一些胎盘细胞因子的异常表达。滋养层细胞产生许多免疫调节剂，在胎盘发育和妊娠维持中发挥作用。我们假设，FIV 感染可能导致滋养层免疫调节剂表达失调，这些分子的异常表达可能增强炎症反应并导致妊娠失败。本项目的目的是评估代表性前炎性细胞因子（TNF-α、IFN-γ、IL-1β、IL-2、IL-6、IL-12p35、IL-12p40、IL-18 和 GM-CSF）和抗炎细胞因子（IL-4、IL-5 和 IL-10）；CD134，一种在激活的 T 细胞上表达的二级共刺激分子（FIV 的主要受体）；趋化因子受体 CXCR4（FIV 的共受体）；趋化因子配体 SDF-1α；以及 FIV gag 在早孕和中孕滋养层中的表达。
我们使用抗细胞角蛋白抗体在免疫组织化学中选择性地识别滋养层细胞，使用激光捕获显微切割收集这些细胞，并从捕获的细胞群体中提取总 RNA。实时、逆转录 PCR 用于定量基因表达。
我们在早孕和中孕滋养层中检测到 IL-4、IL-5、IL-6、IL-1β、IL-12p35、IL-12p40 和 CXCR4。在正常组织中，细胞因子的表达从早孕到中孕增加。在妊娠的任何阶段，FIV 感染的母猫的滋养层中都没有明显的前炎性微环境。繁殖失败伴随着前炎性和抗炎性细胞因子表达的下调。在滋养层中未检测到 CD134，在从感染 FIV 的母猫收集的 10 个滋养层标本中仅检测到一个 FIV gag。
猫的滋养层表达一系列前炎性和抗炎性免疫调节剂，其在正常组织中的表达从早孕到中孕增加。在其他物种中，调节滋养层浸润的免疫调节剂表达减少与不可存活的妊娠有关。在滋养层中很少检测到 FIV RNA，这表明 FIV 感染母猫的高繁殖失败率不是病毒在滋养层中复制的直接结果。在感染 FIV 的猫中，胎盘免疫细胞对滋养层功能和妊娠维持的影响需要进一步研究。
