感染李斯特菌的髓样树突状细胞产生干扰素-β，引发T细胞活化。

Listeria-infected myeloid dendritic cells produce IFN-beta, priming T cell activation.

作者信息

Feng Hanping, Zhang Dong, Palliser Deborah, Zhu Pengcheng, Cai Shenghe, Schlesinger Ann, Maliszewski Laura, Lieberman Judy

机构信息

CBR Institute for Biomedical Research and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.

出版信息

J Immunol. 2005 Jul 1;175(1):421-32. doi: 10.4049/jimmunol.175.1.421.

DOI:10.4049/jimmunol.175.1.421

PMID:15972676

Abstract

The intracellular bacterium Listeria monocytogenes infects dendritic cells (DC) and other APCs and induces potent cell-mediated protective immunity. However, heat-killed bacteria fail to do so. This study explored whether DC differentially respond to live and killed Listeria and how this affects T cell activation. To control for bacterial number, a replication-deficient strain, Lmdd, defective in D-alanine biosynthesis, was used. We found that DC internalize both live and heat-killed Lmdd and similarly up-regulate the expression of costimulatory molecules, a necessary step for T cell activation. However, only live Lmdd-infected DC stimulate T cells to express the early activation marker CD69 and enhance T cell activation upon TCR engagement. Infection with live, but not heat-killed, Lmdd induces myeloid DC to secrete copious amounts of IFN-beta, which requires bacterial cytosolic invasion. Exposure to high concentrations of IFN-beta sensitizes naive T cells for Ag-dependent activation.

摘要

细胞内细菌单核细胞增生李斯特菌感染树突状细胞（DC）和其他抗原呈递细胞（APC），并诱导强大的细胞介导的保护性免疫。然而，热灭活的细菌却无法做到这一点。本研究探讨了DC对活的和灭活的李斯特菌是否有不同反应，以及这如何影响T细胞活化。为了控制细菌数量，使用了一种在D-丙氨酸生物合成方面有缺陷的复制缺陷菌株Lmdd。我们发现DC内化活的和热灭活的Lmdd，并且同样上调共刺激分子的表达，这是T细胞活化的必要步骤。然而，只有感染活Lmdd的DC刺激T细胞表达早期活化标志物CD69，并在TCR参与时增强T细胞活化。感染活的而非热灭活的Lmdd诱导髓样DC分泌大量的IFN-β，这需要细菌胞质入侵。暴露于高浓度的IFN-β会使幼稚T细胞对抗原依赖性活化敏感。