Induced pluripotent stem cell derived macrophages as a cellular system to study salmonella and other pathogens.
Induced pluripotent stem cell derived macrophages as a cellular system to study salmonella and other pathogens.
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DOI：
10.1371/journal.pone.0124307
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Mukhopadhyay S
中科院分区：
文献类型：
--
作者：
Hale C;Yeung A;Goulding D;Pickard D;Alasoo K;Powrie F;Dougan G;Mukhopadhyay S
许多病原体，包括一些人类限制性生物，在巨噬细胞（m - φs）内持续存在和复制是发病的关键步骤。由于缺乏适当的模型系统，人们对这种受宿主限制的细胞内适应的机制知之甚少。在这里，我们探索人类诱导多能干细胞衍生的巨噬细胞（iPSDMs）研究这种病原体相互作用的潜力。我们发现iPSDMs表达一系列已建立的m - φ特异性标记，产生细胞因子，并在IFN-γ和IL-4刺激下分别极化为经典激活状态和替代激活状态。iPSDMs还能有效地吞噬灭活的细菌颗粒以及活的伤寒沙门氏菌和鼠伤寒沙门氏菌，并能杀死这些病原体。我们得出结论，iPSDMs可以支持生产性沙门氏菌感染，并将其作为研究宿主/病原体相互作用的灵活系统。此外，iPSDMs可以为评估多种遗传背景下的宿主反应提供一个灵活实用的细胞平台。
A number of pathogens, including several human-restricted organisms, persist and replicate within macrophages (Mφs) as a key step in pathogenesis. The mechanisms underpinning such host-restricted intracellular adaptations are poorly understood, in part, due to a lack of appropriate model systems. Here we explore the potential of human induced pluripotent stem cell derived macrophages (iPSDMs) to study such pathogen interactions. We show iPSDMs express a panel of established Mφ-specific markers, produce cytokines, and polarise into classical and alternative activation states in response to IFN-γ and IL-4 stimulation, respectively. iPSDMs also efficiently phagocytosed inactivated bacterial particles as well as live Salmonella Typhi and S. Typhimurium and were able to kill these pathogens. We conclude that iPSDMs can support productive Salmonella infection and propose this as a flexible system to study host/pathogen interactions. Furthermore, iPSDMs can provide a flexible and practical cellular platform for assessing host responses in multiple genetic backgrounds.
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DOI：
10.1073/pnas.1207889109
发表时间：
2012-10-30
影响因子：
11.1
作者：
Panicker, Leelamma M.;Miller, Diana;Feldman, Ricardo A.
通讯作者：
Feldman, Ricardo A.
影响因子：
5.2
作者：
Panicker, Leelamma M.;Miller, Diana;Feldman, Ricardo A.
通讯作者：
Feldman, Ricardo A.
影响因子：
4.4
作者：
Haga, Eriko;Endo, Yuko;Senju, Satoru
通讯作者：
Senju, Satoru
影响因子：
5.5
作者：
Mukhopadhyay, S;Peiser, L;Gordon, S
通讯作者：
Gordon, S
影响因子：
3.1
作者：
Weinstein, DL;O'Neill, BL;Metcalf, ES
通讯作者：
Metcalf, ES