Nitric Oxide Production and Effects in Group B Streptococcus Chorioamnionitis.
Nitric Oxide Production and Effects in Group B Streptococcus Chorioamnionitis.
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DOI：
10.3390/pathogens11101115
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发表时间：
2022-09-28
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影响因子：
--
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由B族链球菌（GBS）引起的宫内感染或绒毛膜炎是流产和早产的常见原因。为了引起绒毛膜炎，GBS必须绕过母胎先天免疫防御，包括一氧化氮（NO），一氧化氮合酶（NOS）产生的杀微生物气体。本研究探讨了胎盘NO的生产及其在宿主-病原体相互作用在GBS绒毛膜炎的作用。在上行性GBS绒毛膜炎的小鼠模型中，通过RT-qPCR定量的胎盘NOS同种型表达显示诱导型NOS的表达增加了4倍，内皮型NOS的表达没有显著变化，而神经元型NOS的表达减少。这些NOS表达结果在与GBS共孵育的新鲜收集的人胎盘样品中离体重现。野生型C57 BL/6小鼠GBS绒毛膜炎胎盘的免疫组化显示，在交界区和脓肿区域有弥漫性诱导型NOS表达和高表达灶。野生型和诱导型NOS缺陷小鼠之间的妊娠结局没有显着差异，但野生型母鼠有更频繁的早产的趋势。我们还确定了GBS在富含NO的环境中生存的可能分子机制。在体外暴露的GBS NO导致剂量依赖性的生长抑制，不同的血清型。对具有不同NO抗性表型的两种GBS菌株的RNA-seq显示，这两种GBS菌株共享在NO暴露期间差异表达的几种解毒途径。这些结果表明，胎盘对GBS绒毛膜炎的免疫反应包括诱导的NO产生，并表明GBS激活保守的应激途径，以响应NO暴露。
Intrauterine infection, or chorioamnionitis, due to group B Streptococcus (GBS) is a common cause of miscarriage and preterm birth. To cause chorioamnionitis, GBS must bypass maternal-fetal innate immune defenses including nitric oxide (NO), a microbicidal gas produced by nitric oxide synthases (NOS). This study examined placental NO production and its role in host-pathogen interactions in GBS chorioamnionitis. In a murine model of ascending GBS chorioamnionitis, placental NOS isoform expression quantified by RT-qPCR revealed a four-fold expression increase in inducible NOS, no significant change in expression of endothelial NOS, and decreased expression of neuronal NOS. These NOS expression results were recapitulated ex vivo in freshly collected human placental samples that were co-incubated with GBS. Immunohistochemistry of wild type C57BL/6 murine placentas with GBS chorioamnionitis demonstrated diffuse inducible NOS expression with high-expression foci in the junctional zone and areas of abscess. Pregnancy outcomes between wild type and inducible NOS-deficient mice did not differ significantly although wild type dams had a trend toward more frequent preterm delivery. We also identified possible molecular mechanisms that GBS uses to survive in a NO-rich environment. In vitro exposure of GBS to NO resulted in dose-dependent growth inhibition that varied by serovar. RNA-seq on two GBS strains with distinct NO resistance phenotypes revealed that both GBS strains shared several detoxification pathways that were differentially expressed during NO exposure. These results demonstrate that the placental immune response to GBS chorioamnionitis includes induced NO production and indicate that GBS activates conserved stress pathways in response to NO exposure.
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影响因子：
3.1
作者：
Hooven TA;Catomeris AJ;Bonakdar M;Tallon LJ;Santana-Cruz I;Ott S;Daugherty SC;Tettelin H;Ratner AJ
通讯作者：
Ratner AJ
DOI：
10.1016/0002-9378(95)90324-0
发表时间：
1995-09-01
影响因子：
9.8
作者：
GHABOUR, MS;EIS, ALW;MYATT, L
通讯作者：
MYATT, L
影响因子：
6.4
作者：
Hensler, ME;Liu, GY;Heldt, GP
通讯作者：
Heldt, GP
DOI：
10.1128/genomea.01338-14
发表时间：
2014-12-24
期刊：
Genome announcements
影响因子：
--
作者：
Hooven TA;Randis TM;Daugherty SC;Narechania A;Planet PJ;Tettelin H;Ratner AJ
通讯作者：
Ratner AJ
影响因子：
6.7
作者：
Grosser MR;Paluscio E;Thurlow LR;Dillon MM;Cooper VS;Kawula TH;Richardson AR
通讯作者：
Richardson AR