Helicobacter pylori infection in the stomach induces neuroinflammation: the potential roles of bacterial outer membrane vesicles in an animal model of Alzheimer's disease.
Helicobacter pylori infection in the stomach induces neuroinflammation: the potential roles of bacterial outer membrane vesicles in an animal model of Alzheimer's disease.
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DOI：
10.1186/s41232-022-00224-8
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发表时间：
2022-09-05
影响因子：
8.1
通讯作者：
中科院分区：
文献类型：
--
作者：
幽门螺杆菌（HP）是一种革兰氏阴性菌，长期在人胃中定植。HP在胃黏膜的定植不仅引起胃肠道疾病，还与胃外疾病有关，如特发性血小板减少性紫癜和神经系统疾病。在神经系统疾病中，流行病学研究表明，HP感染可增加阿尔茨海默病（AD）和帕金森病（PD）的患病率。由于HP不侵犯中枢神经系统（CNS），因此人们认为HP感染引起的全身免疫改变可能在AD和PD中起致病作用。在此，我们研究了HP感染对体内和体外中枢神经系统的影响。在中枢神经系统中，慢性HP感染小鼠有小胶质细胞激活，但没有HP定植，尽管没有观察到全身免疫变化。这使我们探讨了hp衍生的外膜囊泡（HP-OMVs）引起神经炎症的可能性。omv是从革兰氏阴性菌的外膜释放到细胞外空间的小球形双层囊泡（20-500 nm）；omv含有脂多糖、蛋白质、肽聚糖、DNA和RNA。omv也被证明在体外激活先天和获得性免疫细胞，并破坏胃上皮的紧密连接（“漏肠”），以及在体内穿过血脑屏障。因此，理论上，只要omv进入体循环，就可以激活远端器官的免疫反应，包括淋巴器官和中枢神经系统。从感染hp的小鼠血清的外泌体部分，我们检测到hp特异性DNA，提示hp - omv的存在。我们还发现，体外hp - omv培养的小胶质细胞增加了细胞增殖、炎症细胞因子的产生和迁移。另一方面，HP-OMVs在体外抑制神经母细胞瘤细胞的增殖。最后，我们发现感染HP的AD模型小鼠体内在活化的小胶质细胞和星形胶质细胞附近有淀粉样斑块。基于文献综述和我们的实验数据，我们提出了我们的工作假设，即肠道慢性HP感染中产生的omv诱导中枢神经系统的神经炎症，解释了HP感染人群中AD患病率较高的原因。
Helicobacter pylori (HP) is a Gram-negative bacterium that colonizes the human stomach chronically. Colonization of HP in the gastric mucosa not only causes gastrointestinal diseases, but also is associated with extra-gastric diseases, such as idiopathic thrombocytopenic purpura and neurological diseases. Among neurological diseases, epidemiological studies have shown that HP infection increases the prevalence of Alzheimer’s disease (AD) and Parkinson’s disease (PD). Since HP does not invade the central nervous system (CNS), it has been considered that systemic immunological changes induced by HP infection may play pathogenic roles in AD and PD. Here, we investigated the effects of HP infection on the CNS in vivo and in vitro. In the CNS, chronically HP-infected mice had microglial activation without HP colonization, although systemic immunological changes were not observed. This led us to explore the possibility that HP-derived outer membrane vesicles (HP-OMVs) could cause neuroinflammation. OMVs are small, spherical bilayer vesicles (20–500 nm) released into the extracellular space from the outer membrane of Gram-negative bacteria; OMVs contain lipopolysaccharide, proteins, peptidoglycan, DNA, and RNA. OMVs have also been shown to activate both innate and acquired immune cells in vitro, and to disrupt the tight junctions of the gastric epithelium (“leaky gut”) as well as cross the blood-brain barrier in vivo. Thus, in theory, OMVs can activate immune responses in the remote organs, including the lymphoid organs and CNS, if only OMVs enter the systemic circulation. From the exosome fraction of sera from HP-infected mice, we detected HP-specific DNA, suggesting the presence of HP-OMVs. We also found that microglia incubated with HP-OMVs in vitro increased the cell proliferation, inflammatory cytokine production, and migration. On the other hand, HP-OMVs suppressed the cell proliferation of neuroblastoma in vitro. Lastly, we found that AD model mice infected with HP had amyloid plaques adjacent to activated microglia and astrocytes in vivo. Based on the literature review and our experimental data, we propose our working hypothesis that OMVs produced in chronic HP infection in the gut induce neuroinflammation in the CNS, explaining the higher prevalence of AD in HP-infected people.
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影响因子：
15.1
作者：
Jaeger, Laura B.;Dohgu, Shinya;Sultana, Rukhsana;Lynch, Jessica L.;Owen, Joshua B.;Erickson, Michelle A.;Shah, Gul N.;Price, Tulin O.;Fleegal-Demotta, Melissa A.;Butterfiled, D. Allan;Banks, William A.
通讯作者：
Banks, William A.
影响因子：
5
作者：
Ha JY;Choi SY;Lee JH;Hong SH;Lee HJ
通讯作者：
Lee HJ
影响因子：
24.5
作者：
Camilleri, Michael
通讯作者：
Camilleri, Michael
影响因子：
11
作者：
Chang WL;Yeh YC;Sheu BS
通讯作者：
Sheu BS
DOI：
10.1016/j.jalz.2018.04.009
发表时间：
2018-09
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Beydoun MA;Beydoun HA;Elbejjani M;Dore GA;Zonderman AB
通讯作者：
Zonderman AB