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口服表达 aCD11c 的植物乳杆菌可调节细胞免疫,减轻肺炎克雷伯菌感染引起的炎症损伤。

Oral administration of Lactobacillus plantarum expressing aCD11c modulates cellular immunity alleviating inflammatory injury due to Klebsiella pneumoniae infection.

机构信息

College of Animal Science and Technology, Yangtze University, Jingzhou, 434025, China.

College of Agriculture, Yangtze University, Jingzhou, 434025, China.

出版信息

BMC Vet Res. 2024 Sep 7;20(1):399. doi: 10.1186/s12917-024-04248-9.

DOI:10.1186/s12917-024-04248-9
PMID:39244529
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11380324/
Abstract

BACKGROUND

Klebsiella pneumoniae (KP), responsible for acute lung injury (ALI) and inflammation of the gastrointestinal tract, is a zoonotic pathogen that poses a threat to livestock farming worldwide. Nevertheless, there is currently no validated vaccine to prevent KP infection. The development of mucosal vaccines against KP using Lactobacillus plantarum (L. plantarum) is an effective strategy.

RESULTS

Firstly, the L. plantarum strains NC8-pSIP409-aCD11c' and NC8-pLc23-aCD11c were constructed via homologous recombination to express the aCD11c protein either inducibly or constitutively. Both NC8-pSIP409-aCD11c' and NC8-pLc23-aCD11c strains could enhance the adhesion and invasion of L. plantarum on bone marrow-derived dendritic cells (BMDCs), and stimulate the activation of BMDCs compared to the control strain NC8-pSIP409 in vitro. Following oral immunization of mice with NC8-pSIP409-aCD11c' and NC8-pLc23-aCD11c, the cellular, humoral, and mucosal immunity were significantly improved, as evidenced by the increased expression of CD4 IL-4 T cells in the spleen, IgG in serum, and secretory IgA (sIgA) in the intestinal lavage fluid (ILF). Furthermore, the protective effects of L. plantarum against inflammatory damage caused by KP infection were confirmed by assessing the bacterial loads in various tissues, lung wet/dry ratio (W/D), levels of inflammatory cytokines, and histological evaluation, which influenced T helper 17 (Th17) and regulatory T (Treg) cells in peripheral blood and lung.

CONCLUSIONS

Both the inducible and constitutive L. plantarum strains NC8-pSIP409-aCD11c' and NC8-pLc23-aCD11c have been found to stimulate cellular and humoral immunity levels and alleviate the inflammatory response caused by KP infection. These findings have provided a basis for the development of a novel vaccine against KP.

摘要

背景

肺炎克雷伯菌(KP)是一种引起急性肺损伤(ALI)和胃肠道炎症的动物源性致病菌,对全球畜牧业构成威胁。然而,目前尚无针对 KP 感染的有效疫苗。使用植物乳杆菌(L. plantarum)开发针对 KP 的黏膜疫苗是一种有效的策略。

结果

首先,通过同源重组构建了表达 aCD11c 蛋白的 L. plantarum 菌株 NC8-pSIP409-aCD11c'和 NC8-pLc23-aCD11c,分别为诱导型和组成型表达。与对照菌株 NC8-pSIP409 相比,NC8-pSIP409-aCD11c'和 NC8-pLc23-aCD11c 菌株均能增强 L. plantarum 对骨髓来源树突状细胞(BMDCs)的黏附和侵袭,并刺激 BMDCs 的活化。经口免疫 NC8-pSIP409-aCD11c'和 NC8-pLc23-aCD11c 后,显著改善了细胞、体液和黏膜免疫,脾内 CD4+IL-4+T 细胞表达增加、血清 IgG 增加、肠灌洗液(ILF)中分泌型 IgA(sIgA)增加。此外,通过评估组织细菌负荷、肺湿/干重比(W/D)、炎症细胞因子水平和组织学评价,证实了 L. plantarum 对 KP 感染引起的炎症损伤的保护作用,这影响了外周血和肺中的辅助性 T 细胞 17(Th17)和调节性 T(Treg)细胞。

结论

诱导型和组成型 L. plantarum 菌株 NC8-pSIP409-aCD11c'和 NC8-pLc23-aCD11c 均能刺激细胞和体液免疫水平,并减轻 KP 感染引起的炎症反应。这些发现为开发新型 KP 疫苗提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fed/11380324/ecb697b1ff70/12917_2024_4248_Fig7_HTML.jpg
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