Department of Medicine, College of Medicine, Korea University, Seoul, South Korea.
Department of Microbiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, South Korea.
Front Immunol. 2020 Dec 8;11:604413. doi: 10.3389/fimmu.2020.604413. eCollection 2020.
, an intracellular bacterium, may cause life-threatening pneumonia in immunocompromised individuals. Mononuclear cells and antibodies have been reported to be associated with the host defense response against This study is to determine whether peptidoglycan-associated lipoprotein (PAL)-specific CD8 T cells are directly associated with protection against , with a focus on potential epitopes. Synthetic peptides derived from PAL of were obtained and tested through in and cytotoxic T lymphocyte (CTL) assays for immunogenicity. PAL DNA vaccines or a peptide epitope with or without CpG-oligodeoxynucleotides (ODN) was evaluated for protection against infection in animal models. When mice were immunized with DNA vaccines expressing the PAL of , they were significantly protected against a lethal challenge with through induction of antigen-specific CD8 CTLs. Of the 13 PAL peptides tested, PAL (EYLKTHPGA) was the most immunogenic and induced the strongest CTL responses. When mice were immunized with the PAL peptide plus CpG-ODN, they were protected against the lethal challenge, while control mice died within 3-6 days after the challenge. Consistent with lung tissue histological data, bacterial counts in the lungs of immunized mice were significantly lower than those in control mice. Also, the amino acid sequence of PAL peptides is conserved among various species. To our knowledge, this study is the first to demonstrate that PAL-specific CD8 T cells play a central role in the host defense response against .
细胞内细菌 可能导致免疫功能低下个体发生危及生命的肺炎。单核细胞和抗体已被报道与宿主防御反应有关 本研究旨在确定肽聚糖相关脂蛋白(PAL)特异性 CD8 T 细胞是否直接与针对 的保护有关,重点是潜在的表位。从 中获得 PAL 的合成肽,并通过在 和细胞毒性 T 淋巴细胞(CTL)测定中进行免疫原性测试。评估 PAL DNA 疫苗或具有或不具有 CpG-寡脱氧核苷酸(ODN)的肽表位,以预防动物模型中 感染。当用表达 PAL 的 DNA 疫苗免疫小鼠时,通过诱导抗原特异性 CD8 CTL,它们显著免受致命的 挑战。在测试的 13 个 PAL 肽中,PAL(EYLKTHPGA)是最具免疫原性的,诱导最强的 CTL 反应。当用 PAL 肽加 CpG-ODN 免疫小鼠时,它们受到保护,免受致命挑战,而对照小鼠在挑战后 3-6 天内死亡。与肺部组织学数据一致,免疫小鼠肺部的细菌计数明显低于对照小鼠。此外,各种 种的 PAL 肽的氨基酸序列是保守的。据我们所知,这项研究首次表明 PAL 特异性 CD8 T 细胞在宿主防御反应中起着核心作用 。