Placental Viral Infection Sensitizes to Endotoxin-Induced Pre-Term Labor: A Double Hit Hypothesis
Placental Viral Infection Sensitizes to Endotoxin-Induced Pre-Term Labor: A Double Hit Hypothesis
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DOI：
10.1111/j.1600-0897.2010.00908.x
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发表时间：
2011-02-01
影响因子：
3.6
通讯作者：
Means, Robert E.
中科院分区：
文献类型：
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作者：
Cardenas, Ingrid;Mor, Gil;Means, Robert E.
在孕妇中，获得性病毒感染并发细菌感染是导致预后不良的一个不利因素。我们评估的影响，病毒感染，不导致早产对低剂量的脂多糖（LPS）的反应。我们的目标是(1)确定病毒感染同时暴露于微生物产品对妊娠结局的影响，(2)确定胎盘和胎儿对病毒致敏LPS的免疫反应。方法c57b /6野生型小鼠在E8.5时注射小鼠γ疱疹病毒68 （MHV68）。在E15.5分注射PBS或LPS。通过多重因素分析妊娠结局和着床部位的细胞因子/趋化因子谱。结果经slps处理的mhv -68感染小鼠100%发生早产和胎儿死亡。早产的特点是促炎细胞因子和趋化因子在胎盘和蜕膜上调。在mhv -68感染的人原代滋养细胞和滋养细胞细胞系中观察到类似的LPS反应。结论我们首次报道了亚临床病毒感染妊娠小鼠可能对细菌感染致敏导致早产。我们提出了“双重打击假说”，即病毒感染的存在增强了怀孕期间细菌产物的影响，不仅导致早产，而且可能导致更大的不良后果。
ProblemAmong pregnant women, acquired viral infections with a concurrent bacterial infection is a detrimental factor associated to poor prognosis. We evaluate the effect of a viral infection that does not lead to pre-term labor on the response to low doses of lipopolysaccharide (LPS). Our objectives were (i) to characterize the effect of a viral infection concurrent with exposure to microbial products on pregnancy outcome and (ii) to characterize the placental and fetal immune responses to the viral sensitization to LPS.MethodC57B/6 wild-type mice were injected with murine gammaherpesvirus 68 (MHV68) at E8.5. Either PBS or LPS was injected i.p. at E15.5. Pregnancy outcome and cytokine/chemokine profile from implantation sites were analyzed by multiplex.ResultsLPS treatment of MHV-68-infected animals induced pre-term delivery and fetal death in 100% of the mice. Pre-term labor was characterized by a upregulation of pro-inflammatory cytokines and chemokines in both placenta and decidua. Similar profiles were observed from MHV-68-infected human primary trophoblast and trophoblast cell lines in response to LPS.ConclusionWe describe for the first time that a sub-clinical viral infection in pregnant mice might sensitize to a bacterial infection leading to pre-term delivery. We propose the 'Double Hit Hypothesis' where the presence of a viral infection enhances the effect of bacterial products during pregnancy leading not only to pre-term labor but likely larger adverse outcomes.