Focal Area Infection Biology, Biozentrum, University of Basel, Basel, Switzerland.
Microbiol Spectr. 2019 Mar;7(2). doi: 10.1128/microbiolspec.BAI-0009-2019.
Systemic infections are a major cause of mortality worldwide and are becoming increasingly untreatable. Recent single-cell data from a mouse model of typhoid fever show that the host immune system actually eradicates many cells, while other organisms thrive at the same time in the same tissue, causing lethal disease progression. The surviving cells have highly heterogeneous metabolism, growth rates, and exposure to various stresses. Emerging evidence suggests that similarly heterogeneous host-pathogen encounters might be a key feature of many infectious diseases. This heterogeneity offers fascinating opportunities for research and application. If we understand the mechanisms that determine the disparate local outcomes, we might be able to develop entirely novel strategies for infection control by broadening successful host antimicrobial attacks and closing permissive niches in which pathogens can thrive. This review describes suitable technologies, a current working model of heterogeneous host- interactions, the impact of diverse subsets on antimicrobial chemotherapy, and major open questions and challenges.
全身性感染是全球范围内主要的致死原因之一，且其治疗难度正日益增加。最近来自伤寒症小鼠模型的单细胞数据表明，宿主免疫系统实际上能够消灭许多细胞，而与此同时，其他生物体在同一组织中茁壮成长，导致致命的疾病进展。存活的细胞具有高度异质的代谢、生长速度和对各种压力的暴露。新出现的证据表明，类似的宿主-病原体异质性接触可能是许多传染病的一个关键特征。这种异质性为研究和应用提供了迷人的机会。如果我们了解决定不同局部结果的机制，我们或许能够通过扩大成功的宿主抗菌攻击并关闭病原体能够茁壮成长的许可小生境，来开发全新的感染控制策略。本文描述了合适的技术、当前的异质宿主相互作用工作模型、不同亚群对抗菌化疗的影响，以及主要的开放性问题和挑战。
