Fetal inflammation induces acute immune tolerance in the neonatal rat hippocampus.
Fetal inflammation induces acute immune tolerance in the neonatal rat hippocampus.
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DOI：
10.1186/s12974-021-02119-w
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发表时间：
2021-03-11
影响因子：
9.3
通讯作者：
Gisslen T
中科院分区：
文献类型：
--
作者：
Singh G;Segura BJ;Georgieff MK;Gisslen T
由于绒毛膜炎而早产的婴儿经常受到胎儿炎症反应综合征（FIRS）的影响，然后受到随后的产后感染。FIRS和出生后全身性炎症事件独立地导致早产儿神经认知结果不良。海马发育的完整性对于早产儿完整的神经认知结果至关重要，并且海马依赖性行为特别容易受到早产儿全身性炎症的影响。FIRS如何调节海马对急性产后炎症事件的免疫反应还不清楚。产前LPS暴露（FIRS）和对照新生大鼠在出生后第5天（P）接受腹腔注射LPS或生理盐水。在P7，通过测量炎性介质和细胞溶质和核NFκB通路蛋白的基因表达来评估四个治疗组的海马中的免疫应答。通过CD 11b+和Iba 1+免疫组织化学（IHC）和分离的小胶质细胞的炎症基因表达来确定小胶质细胞活化。使用GFAP+ IHC测量星形胶质细胞反应性。出生后的LPS导致一个强大的海马炎症反应。相反，产前LPS诱导的FIRS减弱了对出生后LPS暴露的反应，表现为炎症介质基因表达减少，核NFκB p65蛋白减少，活化的CD 11 B+和Iba 1+小胶质细胞减少。孤立的小胶质细胞表现出炎症基因上调出生后的LPS没有证据表明免疫耐受的产前LPS。产前LPS暴露诱导免疫耐受随后出生后LPS暴露在海马。小胶质细胞对出生后的LPS表现出强烈的炎症反应，但只有部分免疫耐受反应。在线版本包含补充材料，可通过10.1186/s12974-021-02119-w获得。
Infants born preterm due to chorioamnionitis are frequently affected by a fetal inflammatory response syndrome (FIRS) and then by subsequent postnatal infections. FIRS and postnatal systemic inflammatory events independently contribute to poor neurocognitive outcomes of preterm infants. Developmental integrity of the hippocampus is crucial for intact neurocognitive outcomes in preterms and hippocampally dependent behaviors are particularly vulnerable to preterm systemic inflammation. How FIRS modulates the hippocampal immune response to acute postnatal inflammatory events is not well understood. Prenatal LPS exposed (FIRS) and control neonatal rats received i.p. LPS or saline at postnatal day (P) 5. On P7, immune response was evaluated in the hippocampus of four treatment groups by measuring gene expression of inflammatory mediators and cytosolic and nuclear NFκB pathway proteins. Microglial activation was determined by CD11b+ and Iba1+ immunohistochemistry (IHC) and inflammatory gene expression of isolated microglia. Astrocyte reactivity was measured using Gfap+ IHC. Postnatal LPS resulted in a robust hippocampal inflammatory response. In contrast, FIRS induced by prenatal LPS attenuated the response to postnatal LPS exposure, evidenced by decreased gene expression of inflammatory mediators, decreased nuclear NFκB p65 protein, and fewer activated CD11b+ and Iba1+ microglia. Isolated microglia demonstrated inflammatory gene upregulation to postnatal LPS without evidence of immune tolerance by prenatal LPS. Prenatal LPS exposure induced immune tolerance to subsequent postnatal LPS exposure in the hippocampus. Microglia demonstrate a robust inflammatory response to postnatal LPS, but only a partial immune tolerance response. The online version contains supplementary material available at 10.1186/s12974-021-02119-w.
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