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鼻腔内免疫重组外膜蛋白 A 诱导对嗜麦芽窄食单胞菌感染的保护性免疫应答。

Intranasal immunization with recombinant outer membrane protein A induces protective immune response against Stenotrophomonas maltophilia infection.

机构信息

No 307 Hospital of PLA of Anhui Medical University, Hefei, China.

Department of Critical Care Medicine, No 307 Hospital of PLA, Beijing, China.

出版信息

PLoS One. 2019 Apr 1;14(4):e0214596. doi: 10.1371/journal.pone.0214596. eCollection 2019.

DOI:10.1371/journal.pone.0214596
PMID:30934008
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6443155/
Abstract

Stenotrophomonas maltophilia (S. maltophilia), a multi-drug resistant opportunistic pathogen, is associated with nosocomial and community-acquired infections. Preventive and therapeutic strategies for such infections are greatly needed. In this study, sequence alignment analysis revealed that Outer membrane protein A (OmpA) was highly conserved among S. maltophilia strains but shared no significant similarity with human and mouse proteomes. In mice, intranasal immunization with S. maltophilia recombinant OmpA (rOmpA) without additional adjuvant induced sustained mucosal and systemic rOmpA-specific antibody responses. Treatment with rOmpA stimulated significantly higher levels of secretion of IFN-γ, IL-2, and IL-17A (All P<0.05) from the primary splenocytes isolated from rOmpA-immunized mice than from the primary splenocytes isolated from PBS-immunized mice. Furthermore, mice immunized with rOmpA showed significantly reduced bacterial burden in the lung and reduced levels of pro-inflammatory cytokines (TNF-α and IL-6) in bronchoalveolar lavage fluid (BALF) 24 hours after intranasal S. maltophilia infection, indicating that immunization with rOmpA may have protective effects against S. maltophilia challenge in mice. Our findings suggest that intranasal immunization with rOmpA may induce mucosal and systemic immune responses in mice, trigger Th1- and Th17-mediated cellular immune responses, and thus stimulate host immune defense against S. maltophilia infection. These results also demonstrate that intranasal vaccination may offer an alternative approach to current strategies since it induces a mucosal as well as a systemic immune response.

摘要

嗜麦芽寡养单胞菌(S. maltophilia)是一种多药耐药的机会性病原体,与医院获得性和社区获得性感染有关。因此,非常需要针对此类感染的预防和治疗策略。在本研究中,序列比对分析表明,外膜蛋白 A(OmpA)在嗜麦芽寡养单胞菌菌株中高度保守,但与人和鼠的蛋白质组没有显著相似性。在小鼠中,鼻腔内免疫接种嗜麦芽寡养单胞菌重组 OmpA(rOmpA)而不添加额外佐剂,可诱导持续的黏膜和系统 rOmpA 特异性抗体反应。rOmpA 治疗可刺激从 rOmpA 免疫小鼠分离的原代脾细胞分泌 IFN-γ、IL-2 和 IL-17A 的水平显著升高(均 P<0.05),而从 PBS 免疫小鼠分离的原代脾细胞则没有。此外,rOmpA 免疫的小鼠在嗜麦芽寡养单胞菌感染后 24 小时,肺中的细菌负荷显著降低,支气管肺泡灌洗液(BALF)中的促炎细胞因子(TNF-α和 IL-6)水平降低,表明 rOmpA 免疫可能对小鼠嗜麦芽寡养单胞菌感染具有保护作用。我们的研究结果表明,鼻腔内免疫接种 rOmpA 可能在小鼠中诱导黏膜和系统免疫反应,触发 Th1 和 Th17 介导的细胞免疫反应,从而刺激宿主对嗜麦芽寡养单胞菌感染的免疫防御。这些结果还表明,鼻腔内疫苗接种可能提供一种替代当前策略的方法,因为它可诱导黏膜和系统免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab8c/6443155/22db88e64110/pone.0214596.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab8c/6443155/14c60136f2ca/pone.0214596.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab8c/6443155/df01cf500a17/pone.0214596.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab8c/6443155/9ebf432c2bf2/pone.0214596.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab8c/6443155/bb593ff86249/pone.0214596.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab8c/6443155/22db88e64110/pone.0214596.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab8c/6443155/14c60136f2ca/pone.0214596.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab8c/6443155/df01cf500a17/pone.0214596.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab8c/6443155/9ebf432c2bf2/pone.0214596.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab8c/6443155/bb593ff86249/pone.0214596.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab8c/6443155/22db88e64110/pone.0214596.g005.jpg

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