Host-directed therapies for bacterial and viral infections.
Host-directed therapies for bacterial and viral infections.
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DOI：
10.1038/nrd.2017.162
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Bartenschlager R
中科院分区：
文献类型：
--
作者：
Kaufmann SHE;Dorhoi A;Hotchkiss RS;Bartenschlager R
宿主导向疗法(HDT)是抗感染药物领域克服耐药性的一种新方法。HDT的目的是干扰病原体复制或持续所需的宿主细胞因子，增强对病原体的保护性免疫反应，减少加重的炎症反应，并平衡病理部位的免疫反应。包括‘休克和杀死’策略或提供重组干扰素的HDTS是治疗艾滋病毒感染的可能方法。抑制由某些急性病毒感染引起的细胞因子风暴的HDTS是一个很有前途的概念。在结核病中，HDT旨在通过吞噬体成熟、自噬和抗菌肽来增强吞噬细胞的抗菌活性。HDTS还通过干扰可溶性(如二十烷类化合物或细胞因子)或细胞(共刺激分子)因子来抑制炎症，并调节肉芽肿以允许抗菌剂的使用或限制组织损伤。在脓毒症和癌症中发生的免疫异常之间的许多相似之处表明，在肿瘤学中有效的HDTS在脓毒症中也可能有希望。免疫表型、基因筛选和生物签名等方面的进展将有助于指导药物治疗以优化宿主的反应。在治疗由耐药病原体引起的新出现的感染和疾病时，规范的病原体导向药物和新型HDTS的组合将成为不可或缺的。本文的在线版本(doi：10.1038/nrd.2017.162)包含补充材料，授权用户可以使用。宿主定向治疗(HDT)旨在干扰病原体复制或持久所需的宿主细胞因子。在这篇综述中，Kaufmannet al.描述用于治疗病毒和细菌感染的HDTS的最新进展，以及将这些方法应用于临床所面临的挑战。本文的在线版本(doi：10.1038/nrd.2017.162)包含补充材料，授权用户可以使用。尽管最近增加了抗病毒药物和抗生素的开发，但抗菌素耐药性和缺乏广谱的病毒靶向药物仍然是重要的问题，迫切需要更多的替代方法来治疗传染病。宿主导向疗法(HDT)是抗感染药物领域的一种新兴方法。HDT背后的策略是干扰病原体复制或持续所需的宿主细胞因子，增强对病原体的保护性免疫反应，减少加重的炎症反应，并平衡病理部位的免疫反应。尽管包含干扰素的HDTS已被很好地用于治疗慢性病毒性肝炎，但旨在功能性治愈持续性病毒感染和开发针对新出现病毒的广谱抗病毒药物的新策略似乎是至关重要的。在结核病等慢性细菌感染中，HDT策略旨在增强吞噬细胞的抗菌活性，并通过干扰可溶性因子(如二十烷类化合物和细胞因子)或细胞因子(如共刺激分子)来抑制炎症。这篇综述描述了目前针对病毒和细菌感染，包括败血症的HDTS的开发进展，以及将这些新方法带入临床所面临的挑战。本文的在线版本(doi：10.1038/nrd.2017.162)包含补充材料，授权用户可以使用。
Host-directed therapy (HDT) is a novel approach in the field of anti-infectives for overcoming antimicrobial resistance. HDT aims to interfere with host cell factors that are required by a pathogen for replication or persistence, to enhance protective immune responses against a pathogen, to reduce exacerbated inflammation and to balance immune reactivity at sites of pathology. HDTs encompassing the 'shock and kill' strategy or the delivery of recombinant interferons are possible approaches to treat HIV infections. HDTs that suppress the cytokine storm that is induced by some acute viral infections represent a promising concept. In tuberculosis, HDT aims to enhance the antimicrobial activities of phagocytes through phagosomal maturation, autophagy and antimicrobial peptides. HDTs also curtail inflammation through interference with soluble (such as eicosanoids or cytokines) or cellular (co-stimulatory molecules) factors and modulate granulomas to allow the access of antimicrobials or to restrict tissue damage. Numerous parallels between the immunological abnormalities that occur in sepsis and cancer indicate that the HDTs that are effective in oncology may also hold promise in sepsis. Advances in immune phenotyping, genetic screening and biosignatures will help to guide drug therapy to optimize the host response. Combinations of canonical pathogen-directed drugs and novel HDTs will become indispensable in treating emerging infections and diseases caused by drug-resistant pathogens. The online version of this article (doi:10.1038/nrd.2017.162) contains supplementary material, which is available to authorized users. Host-directed therapy (HDT) aims to interfere with host cell factors that are required by a pathogen for replication or persistence. In this Review, Kaufmannet al. describe recent progress in the development of HDTs for the treatment of viral and bacterial infections and the challenges in bringing these approaches to the clinic. The online version of this article (doi:10.1038/nrd.2017.162) contains supplementary material, which is available to authorized users. Despite the recent increase in the development of antivirals and antibiotics, antimicrobial resistance and the lack of broad-spectrum virus-targeting drugs are still important issues and additional alternative approaches to treat infectious diseases are urgently needed. Host-directed therapy (HDT) is an emerging approach in the field of anti-infectives. The strategy behind HDT is to interfere with host cell factors that are required by a pathogen for replication or persistence, to enhance protective immune responses against a pathogen, to reduce exacerbated inflammation and to balance immune reactivity at sites of pathology. Although HDTs encompassing interferons are well established for the treatment of chronic viral hepatitis, novel strategies aimed at the functional cure of persistent viral infections and the development of broad-spectrum antivirals against emerging viruses seem to be crucial. In chronic bacterial infections, such as tuberculosis, HDT strategies aim to enhance the antimicrobial activities of phagocytes and to curtail inflammation through interference with soluble factors (such as eicosanoids and cytokines) or cellular factors (such as co-stimulatory molecules). This Review describes current progress in the development of HDTs for viral and bacterial infections, including sepsis, and the challenges in bringing these new approaches to the clinic. The online version of this article (doi:10.1038/nrd.2017.162) contains supplementary material, which is available to authorized users.
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影响因子：
2.6
作者：
Brassard, Paul;Wu, Jennifer W.;Suissa, Samy
通讯作者：
Suissa, Samy
DOI：
10.4049/jimmunol.1201538
发表时间：
2012-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bruns H;Stegelmann F;Fabri M;Döhner K;van Zandbergen G;Wagner M;Skinner M;Modlin RL;Stenger S
通讯作者：
Stenger S
影响因子：
120.7
作者：
Boomer, Jonathan S.;To, Kathleen;Chang, Kathy C.;Takasu, Osamu;Osborne, Dale F.;Walton, Andrew H.;Bricker, Traci L.;Jarman, Stephen D., II;Kreisel, Daniel;Krupnick, Alexander S.;Srivastava, Anil;Swanson, Paul E.;Green, Jonathan M.;Hotchkiss, Richard S.
通讯作者：
Hotchkiss, Richard S.
影响因子：
11.4
作者：
Braaten, D;Luban, J
通讯作者：
Luban, J
影响因子：
32.4
作者：
Colgan, J;Asmal, M;Luban, J
通讯作者：
Luban, J