Loof Torsten G, Rohde Manfred, Chhatwal Gursharan S, Jung Steffen, Medina Eva
Infection Immunology Research Group and Department of Microbial Pathogenesis, Helmholtz Center for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
J Infect Dis. 2007 Dec 15;196(12):1794-803. doi: 10.1086/523647.
Infection with Streptococcus pyogenes remains a significant health care problem. The identification of immune components required for host defenses against S. pyogenes constitutes an important area of research.
Here, we have investigated the role played by dendritic cells (DCs) during infection with S. pyogenes by use of a murine infection model.
Our results show that S. pyogenes induced the maturation of murine DCs, which involved the up-regulation of CD40, CD80, CD86, and major histocompatibility complex class II molecules and the production of interleukin (IL)-12 and tumor necrosis factor-alpha. After subcutaneous infection of mice, S. pyogenes disseminated systemically via the draining lymph nodes. The contribution of DCs to bacterial dissemination was negligible, because most microorganisms were found free in lymph nodes. The contribution of DCs to host defenses against S. pyogenes was investigated using CD11c-diphtheria toxin (DT) receptor (DTR) transgenic mice, in which CD11c(high) cells (conventional DCs) can be transiently depleted in vivo by treatment with low doses of DT. We show that ablation of DCs led to increased bacterial dissemination into draining lymph nodes and systemic organs. Furthermore, ablation of DCs abolished IL-12 production, which is required for effective control of infection.
These data demonstrate that DCs contribute to host defenses against S. pyogenes, likely through the production of IL-12.
化脓性链球菌感染仍是一个重大的医疗保健问题。确定宿主防御化脓性链球菌所需的免疫成分是一个重要的研究领域。
在此，我们通过使用小鼠感染模型研究了树突状细胞（DCs）在化脓性链球菌感染过程中所起的作用。
我们的结果表明，化脓性链球菌诱导小鼠DCs成熟，这涉及CD40、CD80、CD86和主要组织相容性复合体II类分子的上调以及白细胞介素（IL）-12和肿瘤坏死因子-α的产生。小鼠皮下感染后，化脓性链球菌通过引流淋巴结全身播散。DCs对细菌播散的贡献可忽略不计，因为在淋巴结中发现大多数微生物是游离的。使用CD11c-白喉毒素（DT）受体（DTR）转基因小鼠研究了DCs对宿主防御化脓性链球菌的贡献，在这种小鼠中，低剂量DT治疗可在体内短暂清除CD11c（高）细胞（传统DCs）。我们表明，DCs的缺失导致细菌向引流淋巴结和全身器官的播散增加。此外，DCs的缺失消除了IL-12的产生，而IL-12是有效控制感染所必需的。
这些数据表明，DCs可能通过产生IL-12对宿主防御化脓性链球菌做出贡献。
