PDF(Pubmed)
Abstract：
UNASSIGNED: Rupture of the gestational membranes often precedes major pregnancy complications, including preterm labor and preterm birth. One major cause of inflammation in the gestational membranes, chorioamnionitis (CAM) is often a result of bacterial infection. The commensal bacterium Streptococcus agalactiae, or Group B Streptococcus (GBS) is a leading infectious cause of CAM. Obesity is on the rise worldwide and roughly 1 in 4 pregnancy complications is related to obesity, and individuals with obesity are also more likely to be colonized by GBS. The gestational membranes are comprised of several distinct cell layers which are, from outermost to innermost: maternally-derived decidual stromal cells (DSCs), fetal cytotrophoblasts (CTBs), fetal mesenchymal cells, and fetal amnion epithelial cells (AECs). In addition, the gestational membranes have several immune cell populations; macrophages are the most common phagocyte. Here we characterize the effects of palmitate, the most common long-chain saturated fatty acid, on the inflammatory response of each layer of the gestational membranes when infected with GBS, using human cell lines and primary human tissue.
UNASSIGNED: Palmitate itself slightly but significantly augments GBS proliferation. Palmitate and GBS co-stimulation synergized to induce many inflammatory proteins and cytokines, particularly IL-1β and matrix metalloproteinase 9 from DSCs, CTBs, and macrophages, but not from AECs. Many of these findings are recapitulated when treating cells with palmitate and a TLR2 or TLR4 agonist, suggesting broad applicability of palmitate-pathogen synergy. Co-culture of macrophages with DSCs or CTBs, upon co-stimulation with GBS and palmitate, resulted in increased inflammatory responses, contrary to previous work in the absence of palmitate. In whole gestational membrane biopsies, the amnion layer appeared to dampen immune responses from the DSC and CTB layers (the choriodecidua) to GBS and palmitate co-stimulation. Addition of the monounsaturated fatty acid oleate, the most abundant monounsaturated fatty acid in circulation, dampened the proinflammatory effect of palmitate.
UNASSIGNED: These studies reveal a complex interplay between the immunological response of the distinct layers of the gestational membrane to GBS infection and that such responses can be altered by exposure to long-chain saturated fatty acids. These data provide insight into how metabolic syndromes such as obesity might contribute to an increased risk for GBS disease during pregnancy.
UNASSIGNED: Palmitate itself slightly but significantly augments GBS proliferation. Palmitate and GBS co-stimulation synergized to induce many inflammatory proteins and cytokines, particularly IL-1β and matrix metalloproteinase 9 from DSCs, CTBs, and macrophages, but not from AECs. Many of these findings are recapitulated when treating cells with palmitate and a TLR2 or TLR4 agonist, suggesting broad applicability of palmitate-pathogen synergy. Co-culture of macrophages with DSCs or CTBs, upon co-stimulation with GBS and palmitate, resulted in increased inflammatory responses, contrary to previous work in the absence of palmitate. In whole gestational membrane biopsies, the amnion layer appeared to dampen immune responses from the DSC and CTB layers (the choriodecidua) to GBS and palmitate co-stimulation. Addition of the monounsaturated fatty acid oleate, the most abundant monounsaturated fatty acid in circulation, dampened the proinflammatory effect of palmitate.
UNASSIGNED: These studies reveal a complex interplay between the immunological response of the distinct layers of the gestational membrane to GBS infection and that such responses can be altered by exposure to long-chain saturated fatty acids. These data provide insight into how metabolic syndromes such as obesity might contribute to an increased risk for GBS disease during pregnancy.
摘要：
孕膜破裂通常发生在主要妊娠并发症之前，包括早产和早产。孕膜发炎的一个主要原因，绒毛膜羊膜炎（CAM）通常是细菌感染的结果。共生细菌无乳链球菌，或B组链球菌（GBS）是CAM的主要传染性原因。肥胖在全球范围内呈上升趋势，大约四分之一的妊娠并发症与肥胖有关，肥胖个体也更有可能被GBS定植。孕膜由几个不同的细胞层组成，从最外层到最内层：母源蜕膜基质细胞（DSC），胎儿滋养细胞（CTBs），胎儿间充质细胞，和胎儿羊膜上皮细胞（AECs）。此外,孕膜有几种免疫细胞群；巨噬细胞是最常见的吞噬细胞。在这里，我们描述了棕榈酸酯的作用，最常见的长链饱和脂肪酸，感染GBS时，对孕膜各层的炎症反应，使用人类细胞系和原代人类组织。
■棕榈酸盐本身轻微但显著增加GBS增殖。棕榈酸盐和GBS共刺激协同诱导许多炎症蛋白和细胞因子，特别是来自DSC的IL-1β和基质金属蛋白酶9，CTB,和巨噬细胞，但不是来自AEC。当用棕榈酸和TLR2或TLR4激动剂处理细胞时，这些发现中的许多都被概括。表明棕榈酸盐-病原体协同作用的广泛适用性。巨噬细胞与DSC或CTB的共培养，在与GBS和棕榈酸酯共刺激时，导致炎症反应增加，与以前的工作相反，没有棕榈酸盐。在整个孕膜活检中，羊膜层似乎抑制了DSC和CTB层（绒毛膜蜕膜）对GBS和棕榈酸酯共刺激的免疫反应。添加单不饱和脂肪酸油酸酯，循环中最丰富的单不饱和脂肪酸，抑制棕榈酸酯的促炎作用。
■这些研究揭示了孕膜不同层对GBS感染的免疫反应之间的复杂相互作用，并且这种反应可以通过暴露于长链饱和脂肪酸而改变。这些数据提供了有关肥胖等代谢综合征如何导致怀孕期间GBS疾病风险增加的见解。
■棕榈酸盐本身轻微但显著增加GBS增殖。棕榈酸盐和GBS共刺激协同诱导许多炎症蛋白和细胞因子，特别是来自DSC的IL-1β和基质金属蛋白酶9，CTB,和巨噬细胞，但不是来自AEC。当用棕榈酸和TLR2或TLR4激动剂处理细胞时，这些发现中的许多都被概括。表明棕榈酸盐-病原体协同作用的广泛适用性。巨噬细胞与DSC或CTB的共培养，在与GBS和棕榈酸酯共刺激时，导致炎症反应增加，与以前的工作相反，没有棕榈酸盐。在整个孕膜活检中，羊膜层似乎抑制了DSC和CTB层（绒毛膜蜕膜）对GBS和棕榈酸酯共刺激的免疫反应。添加单不饱和脂肪酸油酸酯，循环中最丰富的单不饱和脂肪酸，抑制棕榈酸酯的促炎作用。
■这些研究揭示了孕膜不同层对GBS感染的免疫反应之间的复杂相互作用，并且这种反应可以通过暴露于长链饱和脂肪酸而改变。这些数据提供了有关肥胖等代谢综合征如何导致怀孕期间GBS疾病风险增加的见解。
