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迟发性宿主死亡率和对持久性细胞感染的免疫反应。

Delayed host mortality and immune response upon infection with persister cells.

机构信息

Department of Biological Sciences, Binghamton University , Binghamton, New York, USA.

Binghamton Biofilm Research Center, Binghamton University , Binghamton, New York, USA.

出版信息

Infect Immun. 2023 Oct 17;91(10):e0024623. doi: 10.1128/iai.00246-23. Epub 2023 Sep 21.

Abstract

Chronic infections are a heavy burden on healthcare systems worldwide. Persister cells are thought to be largely responsible for chronic infection due to their tolerance to antimicrobials and recalcitrance to innate immunity factors. is a common and clinically relevant pathogen that contains stereotypical persister cells. Despite their importance in chronic infection, there have been limited efforts to study persister cell infections has a well-described innate immune response similar to that of vertebrates and is a good candidate for the development of an model of infection for persister cells. Similar to what is observed in other bacterial strains, in this work we found that infection with persister cells resulted in a delayed mortality phenotype in , , and compared to infection with regular cells. An in-depth characterization of infected found that bacterial loads differed between persister and regular cells' infections during the early stages. Furthermore, hemocyte activation and antimicrobial peptide expression were delayed/reduced in persister infections over the same time course, indicating an initial suppression of, or inability to elicit, the fly immune response. Overall, our findings support the use of as a model in which to study persister cells where this bacterial subpopulation exhibits delayed virulence and an attenuated immune response.

摘要

慢性感染是全球医疗体系的沉重负担。由于其对抗生素的耐受性和对先天免疫因子的顽固性,持久性细胞被认为是慢性感染的主要原因。 是一种常见且具有临床相关性的病原体,其中包含典型的持久性细胞。尽管它们在慢性感染中很重要,但对持久性细胞感染的研究有限。 具有类似于脊椎动物的明确的先天免疫反应,是开发持久性细胞感染模型的良好候选者。与在其他细菌菌株中观察到的情况类似,在这项工作中,我们发现与常规细胞感染相比, 感染持久性细胞会导致 、 和 的死亡率延迟表型。对感染 的深入表征发现,在早期阶段,持久性细胞和常规细胞感染之间的细菌负荷存在差异。此外,在相同的时间过程中,持久性感染中的血细胞激活和抗菌肽表达延迟/减少,表明初始抑制或无法引发果蝇的免疫反应。总体而言,我们的研究结果支持将 用作研究持久性细胞的模型,其中该细菌亚群表现出延迟的毒力和减弱的免疫反应。

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