孕期母体对聚肌苷酸胞苷酸的反应会导致免疫功能异常和后代行为改变。
Maternal host responses to poly(I:C) during pregnancy leads to both dysfunctional immune profiles and altered behaviour in the offspring.
机构信息
Experimental Therapeutics Laboratory, School of Pharmacy and Medical Science, UniSA Cancer Research Institute, University of South Australia, Adelaide, SA, Australia.
Robinson Research Institute and Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia.
出版信息
Am J Reprod Immunol. 2020 Aug;84(2):e13260. doi: 10.1111/aji.13260. Epub 2020 May 26.
PROBLEM
Autism spectrum disorder (ASD)-like phenotypes in murine models are linked to elevated pro-inflammatory cytokine profiles caused by maternal immune activation (MIA), but whether MIA alters the immune response in the offspring remains unclear.
METHOD OF STUDY
Polyinosinic:polycytidylic acid (poly:[IC]) was used to induce MIA in immunocompetent and control TLR3-deficient pregnant mice, and cytokine levels were measured in maternal and foetal organs. Furthermore, cytokines and behaviour responses were tested after challenge with lipopolysaccharide in 7-day-old and adult mice.
RESULTS
MIA induced on E12 resulted in changes in the cytokine expression profile in maternal and foetal organs and correlated with TNFα and IL-18 dysregulation in immune organs and brains from neonatal mice born to MIA-induced dams. Such changes further correlated with altered behavioural responses in adulthood.
CONCLUSION
MIA induced by pathogens during pregnancy can interfere with the development of the foetal immune and nervous systems leading to dysfunctional immune responses and behaviour in offspring.
问题
母体免疫激活（MIA）引起的促炎细胞因子谱升高与鼠模型中的自闭症谱系障碍（ASD）样表型有关，但 MIA 是否会改变后代的免疫反应尚不清楚。
方法
多聚肌苷酸：多聚胞苷酸（poly:[IC]）用于诱导免疫功能正常和对照 TLR3 缺陷型怀孕小鼠的 MIA，并测量母鼠和胎鼠器官中的细胞因子水平。此外，在 7 天大的和成年小鼠中用脂多糖进行挑战后，测试细胞因子和行为反应。
结果
E12 诱导的 MIA 导致母鼠和胎鼠器官中的细胞因子表达谱发生变化，并与免疫器官和来自 MIA 诱导的母鼠所生新生鼠大脑中的 TNFα 和 IL-18 失调相关。这些变化进一步与成年期行为反应的改变相关。
结论
怀孕期间病原体引起的 MIA 会干扰胎儿的免疫和神经系统发育，导致后代的免疫功能和行为异常。
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