Human Coagulation Factor X-Adenovirus Type 5 Complexes Poorly Stimulate an Innate Immune Response in Human Mononuclear Phagocytes
Human Coagulation Factor X-Adenovirus Type 5 Complexes Poorly Stimulate an Innate Immune Response in Human Mononuclear Phagocytes
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DOI：
10.1128/jvi.03576-14
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发表时间：
2015-03-01
影响因子：
5.4
通讯作者：
Kremer, Eric J.
中科院分区：
文献类型：
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作者：
Eichholz, Karsten;Mennechet, Franck J. D.;Kremer, Eric J.
在脊椎动物中，宿主防御许多病毒的第一道防线之一是先天免疫系统，其使用病原体识别受体（PRR）检测病原体相关分子模式（PAMP）。病原体和宿主之间的动态相互作用在某些情况下产生了种特异性关系。最近，它表明，鼠X因子（mFX）装甲人腺病毒（HAd）刺激mFX-Toll样受体4（TLR 4）相关的反应，在小鼠巨噬细胞在体外和体内。考虑到使用动物进行研究以更好地了解宿主-病原体相互作用的重要性，我们询问人类FX（hFX）-装甲HAd 5型（HAd 5）是否能够激活原代人单核吞噬细胞中的先天免疫传感器。为此，我们测定了人单核吞噬细胞通过TLR/NF-κ B途径，特别是TLR 4途径被hFX-装甲HAd 5刺激的能力。在我们的手中，我们没有发现显着的相互作用，激活，或成熟的人单核吞噬细胞所造成的hFX装甲HAd5.IMPORTANCEAnimals的存在，特别是小鼠，经常被用作信息和强大的代理人病原体如何与自然宿主系统相互作用。如果可能，可以在自然宿主中进行扩展和有针对性的研究。我们的数据将帮助我们了解小鼠临床前测试和人类临床使用的差异，以改善HAd疾病的治疗和Ad载体的有效性。
One of the first lines of host defense against many viruses in vertebrates is the innate immune system, which detects pathogen-associated molecular patterns (PAMPs) using pathogen recognition receptors (PRR). The dynamic interactions between pathogens and hosts create, in some cases, species-specific relationships. Recently, it was shown that murine factor X (mFX)-armored human adenovirus (HAd) stimulated a mFX-Toll-like receptor 4 (TLR4)-associated response in mouse macrophages in vitro and in vivo. Given the importance of studies using animals to better understand host-pathogen interactions, we asked if human FX (hFX)-armored HAd type 5 (HAd5) was capable of activating innate immune sensors in primary human mononuclear phagocytes. To this end, we assayed human mononuclear phagocytes for their ability to be stimulated by hFX-armored HAd5 via a TLR/NF-kappa B pathway, in particular, a TLR4 pathway. In our hands, we found no significant interaction, activation, or maturation of human mononuclear phagocytes caused by the presence of hFX-armored HAd5.IMPORTANCEAnimals, and mice in particular, are often used as informative and powerful surrogates for how pathogens interact with natural host systems. When possible, extended and targeted studies in the natural host can then be performed. Our data will help us understand the differences in preclinical testing in mice and clinical use in humans in order to improve treatment for HAd diseases and Ad vector effectiveness.