Immunomodulator expression in trophoblasts from the feline immunodeficiency virus (FIV)-infected cat.
Immunomodulator expression in trophoblasts from the feline immunodeficiency virus (FIV)-infected cat.
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DOI：
10.1186/1743-422x-8-336
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发表时间：
2011-07-05
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：
Scott VL;Shack LA;Eells JB;Ryan PL;Donaldson JR;Coats KS
在实验条件下，FIV感染经常危及妊娠，并伴有某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。我们推测，FIV感染可能导致滋养细胞免疫调节剂表达失调，这些分子的异常表达可能会加剧炎症并影响妊娠。本项目的目的是评估具有代表性的前α(肿瘤坏死因子-γ、干扰素-β、IL-1α、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(表达在活化T细胞上的次级共刺激分子)、趋化因子受体CXCR4(FIV共受体)、趋化因子配体SDF-1α和FIVGag在早孕和晚期妊娠滋养细胞中的表达。我们使用抗细胞角蛋白抗体在免疫组织化学中选择性地鉴定滋养层细胞，利用激光捕获显微切割收集这些细胞，并从捕获的细胞群中提取总RNA。实时逆转录-聚合酶链式反应(RT-PCR)定量基因表达。我们检测了早孕和晚孕滋养层细胞中IL-4、IL-5、IL-6、IL-1β、IL-12p35、IL-12p40和CXCR4。细胞因子在正常组织中的表达从妊娠早期到妊娠晚期逐渐增加。在妊娠的任何一个阶段，感染FIV的蜂王的滋养层细胞中都没有明显的透明的、促炎的微环境。伴随着生殖失败的是促炎症和抗炎细胞因子的下调。CD134在滋养层细胞中未检测到，从FIV感染的蜂后采集的10份滋养层细胞中只有1份检测到FIV Gag。猫滋养层细胞表达一系列促炎和抗炎免疫调节剂，其在正常组织中的表达从妊娠早期到晚期增加。不能存活的妊娠与免疫调节剂的表达减少有关，免疫调节剂调节其他物种的滋养层侵袭。在滋养层细胞中检测到FIV RNA的情况很少见，这表明FIV感染的蜂王的高繁殖失败率不是滋养层细胞病毒复制的直接结果。胎盘免疫细胞对FIV感染猫的滋养层功能和妊娠维持的影响需要进一步的研究。
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.