Laboratory of Enteric and Sexually Transmitted Diseases, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, Maryland, USA.
Infect Immun. 2012 Aug;80(8):2929-39. doi: 10.1128/IAI.00129-12. Epub 2012 Jun 11.
Campylobacter jejuni is a leading worldwide bacterial cause of human diarrheal disease. Although the specific molecular mechanisms of C. jejuni pathogenesis have not been characterized in detail, host inflammatory responses are thought to be major contributing factors to the resulting typical acute colitis. The intestinal mucosal chemokine response is particularly important in the initial stages of bacterium-induced gut inflammation. Chemokines attract blood phagocytes and lymphocytes to the site of infection and regulate immune cell maturation and the development of localized lymphoid tissues. The production of chemokines by dendritic cells (DCs) following Campylobacter infection has not yet been analyzed. In the current study, we infected human monocyte-derived DCs with C. jejuni to examine the production of key proinflammatory chemokines and chemokine receptors. The chemokines, including CC families (macrophage inflammatory protein 1α [MIP-1α], MIP-1β, RANTES) and CXC families (growth-related oncogene α [GRO-α], IP-10, and monokine induced by gamma interferon [MIG]), were upregulated in Campylobacter-infected DCs. Chemokine receptors CCR6 and CCR7, with roles in DC trafficking, were also induced in Campylobacter-infected DCs. Further, Campylobacter infection stimulated the phosphorylation of P38, P44/42, and stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK) mitogen-activated protein kinases (MAPKs) in DCs. NF-κB activation was specifically involved in chemokine induction in DCs infected with C. jejuni. Additionally, STAT3 was significantly increased in Campylobacter-infected DCs compared to that in uninfected DCs. These results suggest that DCs play a significant role in the initiation and modulation of the inflammatory response by enlisting monocytes, neutrophils, and T lymphocytes during human intestinal infection with Campylobacter.
空肠弯曲菌是导致全球人类腹泻疾病的主要细菌性病原体。虽然空肠弯曲菌发病机制的特定分子机制尚未详细描述，但宿主炎症反应被认为是导致典型急性结肠炎的主要因素。肠道黏膜趋化因子反应在细菌诱导的肠道炎症的初始阶段尤为重要。趋化因子吸引血液中的吞噬细胞和淋巴细胞到感染部位，并调节免疫细胞的成熟和局部淋巴组织的发育。空肠弯曲菌感染后树突状细胞（DC）产生趋化因子的情况尚未进行分析。在本研究中，我们用空肠弯曲菌感染人单核细胞来源的 DC，以研究关键促炎趋化因子和趋化因子受体的产生。趋化因子包括 CC 家族（巨噬细胞炎症蛋白 1α [MIP-1α]、MIP-1β、RANTES）和 CXC 家族（生长相关癌基因α [GRO-α]、IP-10 和γ干扰素诱导的单核细胞趋化蛋白 [MIG]），在空肠弯曲菌感染的 DC 中上调。在空肠弯曲菌感染的 DC 中，也诱导了参与 DC 迁移的趋化因子受体 CCR6 和 CCR7。此外，空肠弯曲菌感染刺激 DC 中 P38、P44/42 和应激激活蛋白激酶/Jun N-末端激酶（SAPK/JNK）丝裂原激活蛋白激酶（MAPK）的磷酸化。NF-κB 激活特异性参与空肠弯曲菌感染的 DC 中趋化因子的诱导。此外，与未感染的 DC 相比，感染空肠弯曲菌的 DC 中 STAT3 显著增加。这些结果表明，在人类空肠弯曲菌感染过程中，DC 通过募集单核细胞、中性粒细胞和 T 淋巴细胞，在炎症反应的启动和调节中发挥重要作用。
