Helicobacter pylori outer membrane vesicles induce astrocyte reactivity through nuclear factor-κappa B activation and cause neuronal damage in vivo in a murine model.
Helicobacter pylori outer membrane vesicles induce astrocyte reactivity through nuclear factor-κappa B activation and cause neuronal damage in vivo in a murine model.
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DOI：
10.1186/s12974-023-02728-7
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发表时间：
2023-03-09
影响因子：
9.3
通讯作者：
中科院分区：
文献类型：
--
作者：
幽门螺杆菌（Hp）感染了世界上50%人口的胃。重要的是，这种细菌的慢性感染与几种胃外病变的出现相关，包括神经退行性疾病。在这种情况下，脑星形胶质细胞变得反应性和神经毒性。然而，目前还不清楚这种高度流行的细菌或它们产生的纳米外膜囊泡（OMV）是否可以到达大脑，从而影响神经元/星形胶质细胞。在这里，我们评估了Hp OMV对星形胶质细胞和神经元在体内和体外的影响。通过质谱法（MS/MS）表征纯化的OMV。标记的OMV经口给药或注射到小鼠尾静脉中以研究OMV-脑分布。通过组织样本的免疫荧光，我们评估了：GFAP（星形胶质细胞）、βIII微管蛋白（神经元）和尿素酶（OMV）。通过监测NF-κB活化、反应性标记物的表达、星形胶质细胞条件培养基（ACM）中的细胞因子和神经元细胞活力来评估OMV在星形胶质细胞中的体外作用。尿素酶和GroEL是OMV中的主要蛋白。尿素酶（OMV）存在于小鼠脑中，其检测与星形胶质细胞反应性和神经元损伤一致。在体外，OMV通过增加中间丝蛋白GFAP和波形蛋白、质膜αVβ3整联蛋白和半通道连接蛋白43诱导星形胶质细胞反应性。OMV还产生神经毒性因子，并以依赖于转录因子NF-κB活化的方式促进IFNγ的释放。反应性星形胶质细胞上的表面抗原，以及响应OMV的分泌因子，显示出抑制神经突生长和损伤神经元。口服或注射到小鼠血流中的OMV到达大脑，改变星形胶质细胞功能并促进体内神经元损伤。OMV对星形胶质细胞的作用在体外得到证实，并显示出NF-κ B依赖性。这些发现表明，Hp可以通过释放纳米囊泡来触发全身效应，这些囊泡穿过上皮屏障并进入CNS，从而改变脑细胞。在线版本包含补充材料，可通过10.1186/s12974-023-02728-7获得。
Helicobacter pylori (Hp) infects the stomach of 50% of the world’s population. Importantly, chronic infection by this bacterium correlates with the appearance of several extra-gastric pathologies, including neurodegenerative diseases. In such conditions, brain astrocytes become reactive and neurotoxic. However, it is still unclear whether this highly prevalent bacterium or the nanosized outer membrane vesicles (OMVs) they produce, can reach the brain, thus affecting neurons/astrocytes. Here, we evaluated the effects of Hp OMVs on astrocytes and neurons in vivo and in vitro. Purified OMVs were characterized by mass spectrometry (MS/MS). Labeled OMVs were administered orally or injected into the mouse tail vein to study OMV-brain distribution. By immunofluorescence of tissue samples, we evaluated: GFAP (astrocytes), βIII tubulin (neurons), and urease (OMVs). The in vitro effect of OMVs in astrocytes was assessed by monitoring NF-κB activation, expression of reactivity markers, cytokines in astrocyte-conditioned medium (ACM), and neuronal cell viability. Urease and GroEL were prominent proteins in OMVs. Urease (OMVs) was present in the mouse brain and its detection coincided with astrocyte reactivity and neuronal damage. In vitro, OMVs induced astrocyte reactivity by increasing the intermediate filament proteins GFAP and vimentin, the plasma membrane αVβ3 integrin, and the hemichannel connexin 43. OMVs also produced neurotoxic factors and promoted the release of IFNγ in a manner dependent on the activation of the transcription factor NF-κB. Surface antigens on reactive astrocytes, as well as secreted factors in response to OMVs, were shown to inhibit neurite outgrowth and damage neurons. OMVs administered orally or injected into the mouse bloodstream reach the brain, altering astrocyte function and promoting neuronal damage in vivo. The effects of OMVs on astrocytes were confirmed in vitro and shown to be NF-κB-dependent. These findings suggest that Hp could trigger systemic effects by releasing nanosized vesicles that cross epithelial barriers and access the CNS, thus altering brain cells. The online version contains supplementary material available at 10.1186/s12974-023-02728-7.
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影响因子：
11
作者：
Chmiela M;Walczak N;Rudnicka K
通讯作者：
Rudnicka K
影响因子：
7.2
作者：
Daneman, Richard;Prat, Alexandre
通讯作者：
Prat, Alexandre
影响因子：
4.4
作者：
Franceschi, Francesco;Gasbarrini, Antonio;Kountouras, Jannis
通讯作者：
Kountouras, Jannis
DOI：
10.1016/j.bbamcr.2016.05.018
发表时间：
2016-09-01
影响因子：
5.1
作者：
Alvarez, Alvaro;Lagos-Cabre, Raul;Leyton, Lisette
通讯作者：
Leyton, Lisette
影响因子：
4.3
作者：
Cellini, Luigina
通讯作者：
Cellini, Luigina