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口服感染的巨噬细胞产生的细胞外囊泡可赋予保护性免疫。

Orally administered extracellular vesicles from -infected macrophages confer protective immunity .

作者信息

Bhimani Saloni, Canas Jorge J, Enslow Samantha M, Mulcare Ryan, Ferraro Mariola J

机构信息

Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, United States.

The Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, United States.

出版信息

Front Immunol. 2025 Aug 15;16:1628756. doi: 10.3389/fimmu.2025.1628756. eCollection 2025.

DOI:10.3389/fimmu.2025.1628756
PMID:40895579
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12394216/
Abstract

is a leading cause of foodborne illness in the United States and worldwide. This enteric pathogen deploys various mechanisms to evade the intestinal mucosal barrier to enhance its survival and further infect systemic tissues. Commercially available vaccines against are currently restricted to the serovar Typhi, while none are currently approved for non-typhoidal (NTS) serovars, which are becoming increasingly resistant to antibiotics. Due to the lack of effective vaccines against NTS infections, novel oral vaccination strategies have garnered significant interest, owing to their protective abilities at the susceptible sites of infection. We previously reported that mice immunized intranasally with small extracellular vesicles (sEVs) derived from infected macrophages protect mice against lethal challenge. In the present study, we used an oral route of administration of sEVs to determine their protective abilities Remarkably, orally administered sEVs from infected macrophages conferred significant host protection, marked by improved survival post-challenge and reduction in tissue bacterial burdens. Additionally, immunized mice exhibited robust serological responses, including elevated levels of both whole- and OmpA-specific IgG antibodies. Collectively, these findings show the potential of orally delivered sEVs as a promising, cell-free vaccine platform for protection against salmonellosis.

摘要

在美国和全球范围内,是食源性疾病的主要病因。这种肠道病原体采用多种机制来逃避肠道黏膜屏障,以提高其存活率并进一步感染全身组织。目前针对的市售疫苗仅限于伤寒血清型,而目前尚无针对非伤寒血清型(NTS)的疫苗获得批准,这些血清型对抗生素的耐药性正在增加。由于缺乏针对NTS感染的有效疫苗,新型口服疫苗策略因其在感染易感部位的保护能力而备受关注。我们之前报道过,用来自感染巨噬细胞的小细胞外囊泡(sEVs)经鼻内免疫小鼠可保护小鼠免受致死性攻击。在本研究中,我们采用口服途径给予sEVs以确定其保护能力。值得注意的是,经口服给予来自感染巨噬细胞的sEVs可赋予宿主显著的保护作用,表现为攻击后存活率提高和组织细菌载量降低。此外,免疫小鼠表现出强烈的血清学反应,包括全特异性和OmpA特异性IgG抗体水平升高。总的来说,这些发现表明口服sEVs作为一种有前景的无细胞疫苗平台用于预防沙门氏菌病的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/12394216/8647fe078519/fimmu-16-1628756-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/12394216/f342dc2e9fd9/fimmu-16-1628756-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/12394216/8d71812aa7e5/fimmu-16-1628756-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/12394216/8647fe078519/fimmu-16-1628756-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/12394216/f342dc2e9fd9/fimmu-16-1628756-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/12394216/8d71812aa7e5/fimmu-16-1628756-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8bb/12394216/8647fe078519/fimmu-16-1628756-g003.jpg

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本文引用的文献

1
On the road: extracellular vesicles in intercellular communication.在路上:细胞间通讯中的细胞外囊泡
Cell Commun Signal. 2025 Feb 18;23(1):95. doi: 10.1186/s12964-024-01999-8.
2
Evaluating small extracellular vesicle-based vaccination across heterologous strains isolated from wastewater.评估从废水中分离出的异源菌株的基于小细胞外囊泡的疫苗接种情况。
Infect Immun. 2025 Feb 18;93(2):e0048524. doi: 10.1128/iai.00485-24. Epub 2025 Jan 13.
3
Chitosan-nanoparticle-based oral Salmonella enteritidis subunit vaccine elicits cross-protection against Salmonella typhimurium in broilers.
壳聚糖纳米粒口服型肠炎沙门氏菌亚单位疫苗对肉鸡的鼠伤寒沙门氏菌具有交叉保护作用。
Poult Sci. 2024 May;103(5):103569. doi: 10.1016/j.psj.2024.103569. Epub 2024 Feb 17.
4
Changes in lipid composition of host-derived extracellular vesicles following infection.感染后宿主来源细胞外囊泡的脂质组成变化。
Microbiol Spectr. 2024 Jan 11;12(1):e0279623. doi: 10.1128/spectrum.02796-23. Epub 2023 Dec 11.
5
Epidemiology of Nontyphoidal Salmonella Bloodstream Infections in Children.儿童非伤寒沙门氏菌血流感染的流行病学。
Pediatrics. 2023 Oct 1;152(4). doi: 10.1542/peds.2023-062357.
6
Outer membrane vesicle-based intranasal vaccines.基于外膜囊泡的鼻内疫苗。
Curr Opin Immunol. 2023 Oct;84:102376. doi: 10.1016/j.coi.2023.102376. Epub 2023 Aug 18.
7
Oral Vaccines: A Better Future of Immunization.口服疫苗:免疫接种的更美好未来。
Vaccines (Basel). 2023 Jul 12;11(7):1232. doi: 10.3390/vaccines11071232.
8
Murine Models of Salmonella Infection.鼠类沙门氏菌感染模型。
Curr Protoc. 2023 Jul;3(7):e824. doi: 10.1002/cpz1.824.
9
Humoral regulation of iron metabolism by extracellular vesicles drives antibacterial response.细胞外囊泡对铁代谢的体液调节驱动抗菌反应。
Nat Metab. 2023 Jan;5(1):111-128. doi: 10.1038/s42255-022-00723-5. Epub 2023 Jan 19.
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Oral delivery of layer-by-layer coated exosomes for colitis therapy.口服层状包裹的外泌体治疗结肠炎。
J Control Release. 2023 Feb;354:635-650. doi: 10.1016/j.jconrel.2023.01.017. Epub 2023 Jan 24.