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噬菌体GADS24对人树突状细胞的免疫调节作用

Immunomodulatory Effects of Phage GADS24 on Human Dendritic Cells.

作者信息

Aldahlawi Alia M, Alsubhi Ghadah A, Alrahimi Jehan S, Basingab Fatemah S, Zaher Kawther A

机构信息

Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 215589, Saudi Arabia.

Immunology Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

出版信息

Biomedicines. 2025 Jun 21;13(7):1519. doi: 10.3390/biomedicines13071519.

DOI:10.3390/biomedicines13071519
PMID:40722595
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12292600/
Abstract

Multidrug-resistant (MDR) () strains pose a significant public health challenge, which has led to the exploration of alternative therapeutic strategies. Due to their antibacterial and immunomodulatory properties, bacteriophages have emerged as promising therapeutic agents. This study investigates the effects of GADS24, a novel lytic bacteriophage of , on human-monocyte-derived dendritic cells (DCs). DCs are exposed to purified GADS24 phage, bacterial lysate, or a combination of both. Flow cytometry was used to assess the expression of surface markers (HLA-DR, CD80, CD83, and CD86), and ELISA was used to measure cytokine production (IL-10 and IL-12p70). Following treatment with bacterial lysate, a significant increase in DC maturation markers was observed. The GADS24 phage alone induced a moderate upregulation of these markers, decreased IL-10 secretion, and increased IL-12p70. Combining bacterial lysate and phage tempered the maturation response compared to the lysate treatment alone. These findings suggest that GADS24 exerts antibacterial activity and modulates host immunity by influencing DC maturation and cytokine production. Due to its dual antimicrobial and immunomodulatory functions, GADS24 is likely to be a valuable adjunctive therapy for multidrug-resistant (MDR) bacterial infections. Furthermore, in vivo studies are necessary to confirm these promising in vitro results.

摘要

多重耐药(MDR)()菌株对公共卫生构成了重大挑战,这促使人们探索替代治疗策略。由于具有抗菌和免疫调节特性,噬菌体已成为有前景的治疗剂。本研究调查了一种新型的溶菌性噬菌体GADS24对人单核细胞衍生树突状细胞(DCs)的影响。将DCs暴露于纯化的GADS24噬菌体、细菌裂解物或两者的组合中。使用流式细胞术评估表面标志物(HLA-DR、CD80、CD83和CD86)的表达,并使用酶联免疫吸附测定法测量细胞因子的产生(IL-10和IL-12p70)。用细菌裂解物处理后,观察到DC成熟标志物显著增加。单独的GADS24噬菌体诱导这些标志物适度上调,减少IL-10分泌,并增加IL-12p70。与单独的裂解物处理相比,将细菌裂解物和噬菌体结合可缓和成熟反应。这些发现表明,GADS24通过影响DC成熟和细胞因子产生发挥抗菌活性并调节宿主免疫。由于其双重抗菌和免疫调节功能,GADS24可能是多重耐药(MDR)细菌感染的一种有价值的辅助治疗方法。此外,需要进行体内研究来证实这些有前景的体外结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29f/12292600/7e214855d7c4/biomedicines-13-01519-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29f/12292600/cefbfc95ec7a/biomedicines-13-01519-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29f/12292600/87fb06792b93/biomedicines-13-01519-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29f/12292600/493ab06acab0/biomedicines-13-01519-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29f/12292600/45d20335a600/biomedicines-13-01519-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29f/12292600/fa6328f8d732/biomedicines-13-01519-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29f/12292600/5c35d9080643/biomedicines-13-01519-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29f/12292600/2f2c2ca967f1/biomedicines-13-01519-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29f/12292600/7e214855d7c4/biomedicines-13-01519-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29f/12292600/cefbfc95ec7a/biomedicines-13-01519-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29f/12292600/87fb06792b93/biomedicines-13-01519-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29f/12292600/7f2c17d0b0ba/biomedicines-13-01519-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29f/12292600/493ab06acab0/biomedicines-13-01519-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29f/12292600/45d20335a600/biomedicines-13-01519-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29f/12292600/fa6328f8d732/biomedicines-13-01519-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29f/12292600/5c35d9080643/biomedicines-13-01519-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29f/12292600/2f2c2ca967f1/biomedicines-13-01519-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b29f/12292600/7e214855d7c4/biomedicines-13-01519-g009.jpg

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Bacteriophage DNA induces an interrupted immune response during phage therapy in a chicken model.
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Phage treatment of Pseudomonas aeruginosa yields a phage-resistant population with different susceptibility to innate immune responses and mild effects on metabolic profiles.噬菌体治疗铜绿假单胞菌会产生对噬菌体具有抗性的群体,该群体对先天免疫反应的敏感性不同,且对代谢谱的影响较小。
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