Dissecting Amyloid Beta Deposition Using Distinct Strains of the Neurotropic Parasite Toxoplasma gondii as a Novel Tool.
Dissecting Amyloid Beta Deposition Using Distinct Strains of the Neurotropic Parasite Toxoplasma gondii as a Novel Tool.
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使用神经寄生虫弓形虫的不同菌株作为一种新工具，将淀粉样ββ沉积解剖。
DOI：
10.1177/1759091417724915
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发表时间：
2017-07
期刊：
影响因子：
4.7
通讯作者：
Koshy AA
中科院分区：
文献类型：
--
作者：
Cabral CM;McGovern KE;MacDonald WR;Franco J;Koshy AA
遗传学和病理学数据表明，由淀粉样前体蛋白加工产生的淀粉样β蛋白(Aβ)是阿尔茨海默病(AD)的主要诱因。为了获得对Aβ调制的新见解，我们试图利用嗜神经性寄生虫弓形虫和哺乳动物大脑之间的共同进化的力量。先前的两项研究将弓形虫对Aβ的相关保护归因于抗炎细胞因子(转化生长因子β和IL-10)的增加和吞噬细胞的渗入。这些研究只使用了一种弓形虫菌株，因此很难确定所提到的变化是与Aβ保护有关，还是仅仅与感染有关。为了解决这个局限性，我们用每一种遗传上不同的、规范的弓形虫菌株(I型、II型或III型)感染了第三个人类淀粉样前体蛋白AD小鼠模型(J20)。然后，我们评估了中枢神经系统的Aβ沉积、免疫细胞反应、全球细胞因子环境和寄生虫负荷。我们发现，尽管II型和III型菌株都建立了慢性中枢神经系统感染和炎症反应，但只有II型感染对Aβ沉积具有保护作用。与未感染和I型感染的小鼠相比，II型和III型感染的小鼠都显示出CNS T细胞和小胶质细胞的数量增加，促炎症细胞因子增加，但两组小鼠的转化生长因子β和IL-10的水平都没有增加两倍。这些数据表明，我们现在可以使用我们对保护性(II型)和非保护性(III型)弓形虫菌株的鉴定来确定哪些寄生虫和宿主因素与Aβ负担的降低有关，而不仅仅是与感染有关。
Genetic and pathologic data suggest that amyloid beta (Aβ), produced by processing of the amyloid precursor protein, is a major initiator of Alzheimer’s disease (AD). To gain new insights into Aβ modulation, we sought to harness the power of the coevolution between the neurotropic parasite Toxoplasma gondii and the mammalian brain. Two prior studies attributed Toxoplasma-associated protection against Aβ to increases in anti-inflammatory cytokines (TGF-β and IL-10) and infiltrating phagocytic monocytes. These studies only used one Toxoplasma strain making it difficult to determine if the noted changes were associated with Aβ protection or simply infection. To address this limitation, we infected a third human amyloid precursor protein AD mouse model (J20) with each of the genetically distinct, canonical strains of Toxoplasma (Type I, Type II, or Type III). We then evaluated the central nervous system (CNS) for Aβ deposition, immune cell responses, global cytokine environment, and parasite burden. We found that only Type II infection was protective against Aβ deposition despite both Type II and Type III strains establishing a chronic CNS infection and inflammatory response. Compared with uninfected and Type I-infected mice, both Type II- and Type III-infected mice showed increased numbers of CNS T cells and microglia and elevated pro-inflammatory cytokines, but neither group showed a >2-fold elevation of TGF-β or IL-10. These data suggest that we can now use our identification of protective (Type II) and nonprotective (Type III) Toxoplasma strains to determine what parasite and host factors are linked to decreased Aβ burden rather than simply with infection.
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影响因子：
4
作者：
Bohrmann, Bernd;Baumann, Karlheinz;Loetscher, Hansruedi
通讯作者：
Loetscher, Hansruedi
影响因子：
14
作者：
Farlow, Martin;Amold, Steven E.;Siemers, Eric R.
通讯作者：
Siemers, Eric R.
影响因子：
82.9
作者：
Baruch, Kuti;Deczkowska, Aleksandra;Schwartz, Michal
通讯作者：
Schwartz, Michal
影响因子：
14
作者：
通讯作者：
--
DOI：
10.4049/jimmunol.1303284
发表时间：
2014-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cekanaviciute E;Dietrich HK;Axtell RC;Williams AM;Egusquiza R;Wai KM;Koshy AA;Buckwalter MS
通讯作者：
Buckwalter MS