Maternal Neutrophil Depletion Fails to Avert Systemic Lipopolysaccharide-Induced Early Pregnancy Defects in Mice.
Maternal Neutrophil Depletion Fails to Avert Systemic Lipopolysaccharide-Induced Early Pregnancy Defects in Mice.
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DOI：
10.3390/ijms22157932
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发表时间：
2021-07-25
影响因子：
5.6
通讯作者：
Paria BC
中科院分区：
文献类型：
--
作者：
Panja S;Benjamin JT;Paria BC
母体感染导致的早孕并发症是由于子宫早期胚泡着床部位(EBIS)免疫环境的紊乱引起的，但其潜在的机制尚不清楚。在这里，我们在一个小鼠模型中证明，正常妊娠从第4天到第6天的进展导致白细胞稳定地从围绕着床胚泡的子宫蜕膜间质带(DSZ)迁移。子宫巨噬细胞CD206+M2-极化。在单核细胞几乎不存在的情况下，单核标记蛋白Ly6C在单核细胞中表达。妊娠第5天全身暴露内毒素导致：(1)快速(2小时)诱导中性粒细胞趋化因子，促进EBIS中大量中性粒细胞的渗透；(2)在2小时内，调节EBIS中调节细胞因子的MyD88(但不是Trif)的mRNA水平迅速升高；(3)妊娠7天时，EBIS出现剂量依赖性缺陷。然而，在脂多糖暴露前使用抗Ly6G抗体清除母体中性粒细胞并不能避免内毒素诱导的EBIS缺陷，这使得我们可以认为依赖TLR4-MyD88的炎症通路的激活参与了内毒素诱导的EBIS缺陷。因此，阻断TLR4-MyD88信号通路的激活可能是预防EBIS感染诱导的病理的一个有趣的方法。
Maternal infection-induced early pregnancy complications arise from perturbation of the immune environment at the uterine early blastocyst implantation site (EBIS), yet the underlying mechanisms remain unclear. Here, we demonstrated in a mouse model that the progression of normal pregnancy from days 4 to 6 induced steady migration of leukocytes away from the uterine decidual stromal zone (DSZ) that surrounds the implanted blastocyst. Uterine macrophages were found to be CD206+ M2-polarized. While monocytes were nearly absent in the DSZ, DSZ cells were found to express monocyte marker protein Ly6C. Systemic endotoxic lipopolysaccharide (LPS) exposure on day 5 of pregnancy led to: (1) rapid (at 2 h) induction of neutrophil chemoattractants that promoted huge neutrophil infiltrations at the EBISs by 24 h; (2) rapid (at 2 h) elevation of mRNA levels of MyD88, but not Trif, modulated cytokines at the EBISs; and (3) dose-dependent EBIS defects by day 7 of pregnancy. Yet, elimination of maternal neutrophils using anti-Ly6G antibody prior to LPS exposure failed to avert LPS-induced EBIS defects allowing us to suggest that activation of Tlr4-MyD88 dependent inflammatory pathway is involved in LPS-induced defects at EBISs. Thus, blocking the activation of the Tlr4-MyD88 signaling pathway may be an interesting approach to prevent infection-induced pathology at EBISs.
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影响因子：
64.8
作者：
Finisguerra V;Di Conza G;Di Matteo M;Serneels J;Costa S;Thompson AA;Wauters E;Walmsley S;Prenen H;Granot Z;Casazza A;Mazzone M
通讯作者：
Mazzone M
影响因子：
6.7
作者：
Fischer MA;Davies ML;Reider IE;Heipertz EL;Epler MR;Sei JJ;Ingersoll MA;Rooijen NV;Randolph GJ;Norbury CC
通讯作者：
Norbury CC
影响因子：
3.7
作者：
Tirado-González I;Barrientos G;Freitag N;Otto T;Thijssen VL;Moschansky P;von Kwiatkowski P;Klapp BF;Winterhager E;Bauersachs S;Blois SM
通讯作者：
Blois SM
影响因子：
--
作者：
Filer, Andrew;Parsonage, Greg;Smith, Emily;Osborne, Chloe;Thomas, Andrew M C;Curnow, S John;Rainger, G Ed;Raza, Karim;Nash, Gerard B;Lord, Janet;Salmon, Mike;Buckley, Christopher D
通讯作者：
Buckley, Christopher D
DOI：
10.1016/j.rinim.2015.12.001
发表时间：
2016-01-01
期刊：
Results in immunology
影响因子：
--
作者：
Bruhn, Kevin W;Dekitani, Ken;Spellberg, Brad
通讯作者：
Spellberg, Brad