Ikonomidis G, Paterson Y, Kos F J, Portnoy D A
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia 19104-6076.
J Exp Med. 1994 Dec 1;180(6):2209-18. doi: 10.1084/jem.180.6.2209.
Listeria monocytogenes is a facultative intracellular pathogen that grows in the cytoplasm of infected host cells. We examined the capacity of L. monocytogenes to introduce influenza nucleoprotein (NP) into the class I pathway of antigen presentation both in vitro and in vivo. Recombinant L. monocytogenes secreting a fusion of listeriolysin O and NP (LLO-NP) targeted infected cells for lysis by NP-specific class I-restricted cytotoxic T cells. Antigen presentation occurred in the context of three different class I haplotypes in vitro. A hemolysin-negative L. monocytogenes strain expressing LLO-NP was able to present in a class II-restricted manner. However, it failed to target infected cells for lysis by CD8+ T cells, indicating that hemolysin-dependent bacterial escape from the vacuole is necessary for class I presentation in vitro. Immunization of mice with a recombinant L. monocytogenes strain that stably expressed and secreted LLO-NP induced NP-specific CD8+ cytotoxic T lymphocytes. These studies have implications for the use of L. monocytogenes to deliver potentially any antigen to the class I pathway in vivo.
单核细胞增生李斯特菌是一种兼性细胞内病原体，可在受感染宿主细胞的细胞质中生长。我们在体外和体内研究了单核细胞增生李斯特菌将流感核蛋白（NP）引入I类抗原呈递途径的能力。分泌溶菌酶O和NP融合蛋白（LLO-NP）的重组单核细胞增生李斯特菌可被NP特异性I类限制性细胞毒性T细胞靶向裂解感染细胞。体外抗原呈递发生在三种不同的I类单倍型背景下。表达LLO-NP的溶血素阴性单核细胞增生李斯特菌菌株能够以II类限制性方式呈递抗原。然而，它不能被CD8+T细胞靶向裂解感染细胞，这表明溶血素依赖性细菌从液泡中逃逸对于体外I类呈递是必要的。用稳定表达和分泌LLO-NP的重组单核细胞增生李斯特菌菌株免疫小鼠可诱导NP特异性CD8+细胞毒性T淋巴细胞。这些研究对于利用单核细胞增生李斯特菌在体内将潜在的任何抗原递送至I类途径具有重要意义。
