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细胞壁缺陷型原生质球对实验性小鼠李斯特菌病的疗效

Efficacy of Cell Wall-Deficient Spheroplasts Against Experimental Murine Listeriosis.

作者信息

Ansari M A, Zia Q, Kazmi S, Ahmad E, Azhar A, Johnson K E, Zubair S, Owais M

机构信息

Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.

Department of Microbiology and Immunology, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.

出版信息

Scand J Immunol. 2015 Jul;82(1):10-24. doi: 10.1111/sji.12296.

DOI:10.1111/sji.12296
PMID:25833403
Abstract

Various strategies adapted to develop an efficient vaccine against foodborne pathogen, Listeria monocytogenes, have met with little success. Spheroplasts (bacterial cell devoid of cell wall) are likely to undergo membrane-membrane fusion, leading to the delivery of their content to the cytosol of antigen-presenting cells, thus facilitating MHC class I antigen processing and presentation. In this study, we evaluated the prophylactic potential of Listeria spheroplast-based vaccine against experimental murine listeriosis in comparison with heat-killed Listeria (HKL) and archaeosome-entrapped Listeria whole-cell protein (LWCP). Compared with HKL, the spheroplast-based vaccine was found to evoke better Th1 response as exhibited by the presence of type 1 cytokines in the host (interferon-γ and IL-12) and a high IgG2a /IgG1 ratio. Robust lympho-proliferative efficacy was apparent in both spheroplast-immunized and archaeosome-entrapped LWCP-immunized groups. The upregulation of costimulatory and effector memory markers upon immunization with spheroplasts was found to be at par with that evoked by archaeosome-entrapped LWCP-immunized group. Central memory response in gated CD8(+) T cell was much higher in spheroplast-immunized animals when compared with archaeosome-entrapped LWCP group. The data presented here clearly demonstrate that spheroplasts evoked a robust immune response and offer better prophylactic potential against L. monocytogenes.

摘要

为研发针对食源性病原体单核细胞增生李斯特菌的高效疫苗而采用的各种策略成效甚微。原生质球(无细胞壁的细菌细胞)可能会发生膜-膜融合,导致其内容物被递送至抗原呈递细胞的胞质溶胶,从而促进MHC I类抗原的加工和呈递。在本研究中,我们评估了基于李斯特菌原生质球的疫苗与热灭活李斯特菌(HKL)和古脂质体包裹的李斯特菌全细胞蛋白(LWCP)相比,对实验性小鼠李斯特菌病的预防潜力。与HKL相比,发现基于原生质球的疫苗能引发更好的Th1反应,宿主中1型细胞因子(干扰素-γ和IL-12)的存在以及高IgG2a /IgG1比值就表明了这一点。在原生质球免疫组和古脂质体包裹的LWCP免疫组中均明显存在强大的淋巴细胞增殖效力。在用原生质球免疫后共刺激和效应记忆标志物的上调情况与古脂质体包裹的LWCP免疫组所引发的情况相当。与古脂质体包裹的LWCP组相比,在原生质球免疫的动物中,门控CD8(+) T细胞中的中枢记忆反应要高得多。此处呈现的数据清楚地表明,原生质球能引发强大的免疫反应,并对单核细胞增生李斯特菌具有更好的预防潜力。

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Efficacy of Cell Wall-Deficient Spheroplasts Against Experimental Murine Listeriosis.细胞壁缺陷型原生质球对实验性小鼠李斯特菌病的疗效
Scand J Immunol. 2015 Jul;82(1):10-24. doi: 10.1111/sji.12296.
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Systemic immunization induces protective CD4+ and CD8+ T cell-mediated immune responses in murine Listeria monocytogenes meningoencephalitis.全身免疫在小鼠单核细胞增多性李斯特菌性脑膜脑炎中诱导保护性CD4+和CD8+ T细胞介导的免疫反应。
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Induction by killed Listeria monocytogenes of effector T cells mediating delayed-type hypersensitivity but not protection in mice.用灭活的单核细胞增生李斯特菌诱导效应T细胞,该效应T细胞介导小鼠的迟发型超敏反应,但不介导保护作用。
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Heat-killed Listeria monocytogenes as an adjuvant converts established murine Th2-dominated immune responses into Th1-dominated responses.热灭活的单核细胞增生李斯特菌作为佐剂可将已建立的以小鼠Th2为主导的免疫反应转变为以Th1为主导的反应。
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Pre-existing anti-Salmonella vector immunity prevents the development of protective antigen-specific CD8 T-cell frequencies against murine listeriosis.预先存在的抗沙门氏菌载体免疫会阻止针对鼠类李斯特菌病产生保护性抗原特异性CD8 T细胞频率。
Microbes Infect. 2007 Oct;9(12-13):1447-53. doi: 10.1016/j.micinf.2007.07.010. Epub 2007 Aug 7.

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