Anosova N G, Chabot S, Shreedhar V, Borawski J A, Dickinson B L, Neutra M R
Department of Medicine, Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
Mucosal Immunol. 2008 Jan;1(1):59-67. doi: 10.1038/mi.2007.7.
The follicle-associated epithelium (FAE) of Peyer's patches (PPs) transports antigens and microorganisms into mucosal lymphoid tissues where they are captured by subepithelial dendritic cells (DCs). Feeding of cholera toxin (CT) induced migration of subepithelial DCs to interfollicular T-cell areas within 24 h. This study investigated short-term effects of CT, Escherichia coli heat-labile toxin, and non-toxic derivatives on DC migration. CT or CTB injected into ligated intestinal loops induced significant increase in CD11c+ DCs within the FAE within 90 min. In mice fed CT intragastrically, DC numbers in the FAE increased by 1 h, were maximal by 2 h, declined between 8 and 12 h, and were reversed by 24 h. Feeding of native LT, recombinant CTB, dibutyryl cyclic AMP, and to a lesser extent mutated CT(E29H) or mutated LT(R192G) had the same effect. Thus, both A and B subunits of enterotoxins, presumably acting through distinct signaling pathways, may promote capture of incoming antigens and pathogens by PP DCs.
派尔集合淋巴结(PP)的滤泡相关上皮(FAE)将抗原和微生物转运至黏膜淋巴组织,在此它们被上皮下树突状细胞(DC)捕获。喂食霍乱毒素(CT)可在24小时内诱导上皮下DC迁移至滤泡间T细胞区。本研究调查了CT、大肠杆菌不耐热毒素及其无毒衍生物对DC迁移的短期影响。将CT或CTB注入结扎的肠袢中,90分钟内FAE内CD11c⁺ DC显著增加。给小鼠灌胃CT后,FAE中的DC数量在1小时时增加,2小时时达到峰值,8至12小时之间下降,24小时时恢复至初始水平。喂食天然LT、重组CTB、二丁酰环磷酸腺苷,以及程度较轻的突变CT(E29H)或突变LT(R192G)均有相同效果。因此,肠毒素的A和B亚基可能通过不同的信号通路发挥作用,均可促进PP DC捕获进入的抗原和病原体。