Campylobacter jejuni induces maturation and cytokine production in human dendritic
Campylobacter jejuni induces maturation and cytokine production in human dendritic
复制标题
DOI：
10.1128/iai.74.5.2697-2705.2006
复制
发表时间：
2006-05-01
影响因子：
3.1
通讯作者：
Kopecko, DJ
中科院分区：
文献类型：
--
作者：
Hu, L;Bray, MD;Kopecko, DJ
空肠弯曲杆菌是发达国家和发展中国家人类腹泻病的主要原因。结肠粘膜侵袭和由此产生的宿主炎症反应被认为是导致这种疾病的痢疾形式的关键因素。树突状细胞（DC）在针对微生物感染的先天性和适应性免疫反应中发挥着重要作用。在本研究中，研究了人单核细胞来源的树突状细胞和空肠弯曲菌之间的相互作用。我们发现空肠弯曲菌在 2 小时内很容易被 DC 内化。然而，空肠弯曲菌长时间感染（24 或 48 小时）后，细胞内仅残留少量活细菌。观察到空肠弯曲菌对树突状细胞的最小细胞毒性。空肠弯曲菌在 24 小时内诱导树突状细胞成熟，细胞表面标记蛋白 CD40、CD80 和 CD86 上调表明。此外，与未感染的 DC 相比，弯曲杆菌感染的 DC 触发了 NF-κ B 的激活，并显着刺激了白细胞介素 1 β (IL-1 β)、IL-6、IL-8、IL-10、IL-12、γ 干扰素和肿瘤坏死因子 α (TNF-α) 的产生。细菌对 DC 的主动入侵对于诱导这些细胞因子来说并不是必需的，因为热灭活的空肠弯曲菌刺激的细胞因子产生水平与活细菌相似。纯化的空肠弯曲菌脂寡糖似乎是 DC 细胞因子产生增加的主要刺激物。总而言之，这些数据表明，在感染过程中，Cantpylobacter 通过增加 IL-1β、IL-6、IL-8 和 TNF-α 的产生来触发先天炎症反应，并启动 Th1 极化的适应性免疫反应，正如根据 IL-12 的高水平产生所预测的那样。
Campylobacter jejuni is a leading bacterial cause of human diarrheal disease in both developed and developing nations. Colonic mucosal invasion and the resulting host inflammatory responses are thought to be the key contributing factors to the dysenteric form of this disease. Dendritic cells (DCs) play an important role in both the innate and adaptive immune responses to microbial infection. In this study, the interaction between human monocyte-derived dendritic cells and C. jejuni was studied. We found that C. jejuni was readily internalized by DCs over a 2-h period. However, after a prolonged infection period (24 or 48 h) with C. jejuni, only a few viable bacteria remained intracellularly. Minimal cytotoxicity of C. jejuni to dendritic cells was observed. C. jejuni induced the maturation of dendritic cells over 24 h, as indicated by up-regulation of cell surface marker proteins CD40, CD80, and CD86. In addition, Campylobacter-infected DCs triggered activation of NF-kappa B and significantly stimulated production of interleukin-1 beta (IL-1 beta), IL-6, IL-8, IL-10, IL-12, gamma interferon, and tumor necrosis factor alpha (TNF-alpha) compared to uninfected DCs. Active bacterial invasion of DCs was not necessary for the induction of these cytokines, as heat-killed C. jejuni stimulated similar levels of cytokine production as live bacteria. Purified lipooligosaccharide of C. jejuni appears to be the major stimulant for the increased production of cytokines by DCs. Taken together, these data indicate that during infection, Cantpylobacter triggers an innate inflammatory response through increased production of IL-1 beta, IL-6, IL-8, and TNF-alpha and initiates a Th1-polarized adaptive immune response as predicted from the high level of production of IL-12.