Zhou Mengying, Jiang Mingjuan, Ren Chenyan, Liu Sijing, Pu Qikang, Goldfine Howard, Shen Hao, Wang Chuan
Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Department of Public Health Laboratory Sciences, West China School of Public Health, Sichuan University Chengdu, China.
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania Philadelphia, PA, USA.
Front Microbiol. 2016 Jun 7;7:790. doi: 10.3389/fmicb.2016.00790. eCollection 2016.
Listeria monocytogenes (LM) vectors have shown much promise in delivery of viral and tumor antigens for the development of vaccines. L. ivanovii (LI) is a closely related bacterium with a similar intracellular life cycle that may offer advantages over LM because it is not a human pathogen, but can infect other animal species. Recent studies show that recombinant LI expressing Mycobacterium tuberculosis antigens is effective in inducing protective immunity in mouse models, demonstrating the potential of LI as a live vaccine vector. However, a key barrier in the development of LI into a live vaccine vector is that its pathogenic and immunogenic characteristics have yet to be fully understood. Therefore, in this research, C57BL/6J mice were inoculated with LM or LI intravenously or intranasally, and bacterial loads, histopathologic changes, and cytokine production were determined at indicated days post inoculation. Results showed that after intravenous infection with LM or LI, bacteria were found proliferating in the liver, spleen, and lung. However, LI could only reach a heavy burden in the liver and its ability to multiply and to resist host immunity seemed limited in the spleen and lung. After intranasal inoculation with LI, bacteria were mainly localized in the lung and failed to infect liver or spleen, while LM could. In organs with heavy LI burden, lesions were isolated, localized and densely packed, compared to lesions caused by LM, which were invasive. In the liver of intravenously inoculated mice and lung of intranasally inoculate mice, LI was able to elicit comparable cytokine production with LM and cause less severe histopathologic damages, and thus could be considered as a vector for treating or preventing hepatic or pulmonary diseases.
单核细胞增生李斯特菌(LM)载体在递送病毒和肿瘤抗原以开发疫苗方面已显示出很大的前景。伊氏李斯特菌(LI)是一种密切相关的细菌,具有相似的细胞内生命周期,它可能比LM具有优势,因为它不是人类病原体,但可以感染其他动物物种。最近的研究表明,表达结核分枝杆菌抗原的重组LI在小鼠模型中能有效诱导保护性免疫,证明了LI作为活疫苗载体的潜力。然而,将LI开发成活疫苗载体的一个关键障碍是其致病和免疫原性特征尚未完全了解。因此,在本研究中,对C57BL/6J小鼠进行静脉内或鼻内接种LM或LI,并在接种后指定天数测定细菌载量、组织病理学变化和细胞因子产生情况。结果显示,静脉内感染LM或LI后,在肝脏、脾脏和肺中发现细菌增殖。然而,LI仅在肝脏中能达到高载量,其在脾脏和肺中的繁殖及抵抗宿主免疫的能力似乎有限。鼻内接种LI后,细菌主要定位于肺部,未能感染肝脏或脾脏,而LM则可以。与LM引起的具有侵袭性的病变相比,在LI载量高的器官中,病变是孤立的、局部的且密集堆积的。在静脉内接种小鼠的肝脏和鼻内接种小鼠的肺中,LI能够引发与LM相当的细胞因子产生,并且引起的组织病理学损伤较轻,因此可被视为治疗或预防肝脏或肺部疾病的载体。