Host-encoded antivirulence defenses: host physiologies teach pathogens to play nice

IF 6.6 2区 医学 Q1 IMMUNOLOGY Current Opinion in Immunology Pub Date : 2024-10-09 DOI:10.1016/j.coi.2024.102472
Janelle S Ayres
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Abstract

Successful treatment of infectious diseases requires a multiprong approach involving strategies that limit pathogen burdens and that limit disease. Traditionally, disease defense is thought to be a direct function of pathogen killing, and thus, our current methods for treating infections have largely relied on pathogen eradication, leading to drug resistance. Strategies that target the virulence of the pathogen, called antivirulence, have been proposed to be a necessary strategy to integrate into our infectious disease toolbox to promote disease defense and alleviate the burden of drug resistance. Traditional antivirulence strategies have largely focused on developing compounds that directly target microbial virulence factors or products to impair their ability to initiate and sustain infection. As virulence is linked to pathogen fitness, simply targeting a virulence factor may not be sufficient to overcome the ability of pathogens evolving resistance. In this review, I discuss co-operative defenses that hosts have evolved to promote antivirulence mechanisms that suppress pathogen virulence without having a negative impact on pathogen fitness. I also discuss the different definitions antivirulence has been assigned over the years and suggest a more holistic one. Co-operative defenses remain an underexplored resource in medicine, and by learning from how hosts have evolved to promote antivirulence, we have the potential to develop disease defense interventions without the risk of pathogens developing drug resistance.
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宿主编码的抗病毒防御系统:宿主生理机能教病原体学会和睦相处。
成功治疗传染病需要采取多管齐下的方法,包括限制病原体负担和限制疾病的策略。传统上,疾病防御被认为是杀死病原体的直接功能,因此,我们目前治疗感染的方法在很大程度上依赖于消灭病原体,从而导致耐药性。针对病原体毒力的策略,即抗病毒策略,已被提出作为一种必要的策略纳入我们的传染病工具箱,以促进疾病防御并减轻耐药性的负担。传统的抗病毒策略主要侧重于开发直接针对微生物毒力因子或产物的化合物,以削弱它们启动和维持感染的能力。由于毒力与病原体的生存能力有关,因此仅仅针对毒力因子可能不足以克服病原体的抗药性进化能力。在这篇综述中,我将讨论宿主为促进抗病毒机制而进化出的合作防御机制,这种机制既能抑制病原体的毒力,又不会对病原体的适应性产生负面影响。我还讨论了多年来对抗病毒的不同定义,并提出了一个更全面的定义。合作防御仍是医学中一种未被充分开发的资源,通过学习宿主如何进化以促进抗病毒性,我们有可能开发出疾病防御干预措施,而无需承担病原体产生抗药性的风险。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
13.30
自引率
1.40%
发文量
94
审稿时长
67 days
期刊介绍: Current Opinion in Immunology aims to stimulate scientifically grounded, interdisciplinary, multi-scale debate and exchange of ideas. It contains polished, concise and timely reviews and opinions, with particular emphasis on those articles published in the past two years. In addition to describing recent trends, the authors are encouraged to give their subjective opinion of the topics discussed. In Current Opinion in Immunology we help the reader by providing in a systematic manner: 1. The views of experts on current advances in their field in a clear and readable form. 2. Evaluations of the most interesting papers, annotated by experts, from the great wealth of original publications. Current Opinion in Immunology will serve as an invaluable source of information for researchers, lecturers, teachers, professionals, policy makers and students. Current Opinion in Immunology builds on Elsevier''s reputation for excellence in scientific publishing and long-standing commitment to communicating reproducible biomedical research targeted at improving human health. It is a companion to the new Gold Open Access journal Current Research in Immunology and is part of the Current Opinion and Research(CO+RE) suite of journals. All CO+RE journals leverage the Current Opinion legacy-of editorial excellence, high-impact, and global reach-to ensure they are a widely read resource that is integral to scientists'' workflow.
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