Rimoldi Monica, Chieppa Marcello, Larghi Paola, Vulcano Marisa, Allavena Paola, Rescigno Maria
Department of Experimental Oncology, European Institute of Oncology, Istituto di Ricerche Farmacologiche, Mario Negri, Milan, Italy.
Blood. 2005 Oct 15;106(8):2818-26. doi: 10.1182/blood-2004-11-4321. Epub 2005 Jul 19.
Dendritic cells (DCs) are able to open the tight junctions between adjacent epithelial cells (ECs) and to take up both invasive and noninvasive bacteria directly from the intestinal lumen. In this study, we describe a tight cross talk between ECs and human monocyte-derived DCs (MoDCs) in bacterial handling across epithelial monolayers. We show that the release of proinflammatory mediators by ECs in response to bacteria is dependent on bacterial invasiveness and on the presence of flagella. This correlates with the capacity of EC-derived factors to modulate MoDC function. MoDCs incubated with supernatants of bacteria-treated ECs are "noninflammatory" as they release interleukin-10 (IL-10) but not IL-12 and can drive only T helper (Th)-2 type T cells. Moreover, noninflammatory MoDCs release chemokines aimed at recruiting Th2 and T-regulatory cells. In contrast, when MoDCs are incubated with ECs and bacteria in a transwell coculture system, and can contact directly the bacteria across stimulated EC monolayers, they are more inflammatory as they release IL-12 and IL-10 and induce both Th1 and Th2 responses. These results suggest that ECs are not simply a barrier to bacteria entering via the oral route, but they actively influence the activating properties of DCs.
树突状细胞（DCs）能够打开相邻上皮细胞（ECs）之间的紧密连接，并直接从肠腔摄取侵袭性和非侵袭性细菌。在本研究中，我们描述了在上皮单层的细菌处理过程中，ECs与人类单核细胞衍生的DCs（MoDCs）之间紧密的相互作用。我们发现，ECs对细菌反应而释放促炎介质取决于细菌的侵袭性和鞭毛的存在。这与EC衍生因子调节MoDC功能的能力相关。用经细菌处理的ECs的上清液孵育的MoDCs是“非炎性的”，因为它们释放白细胞介素-10（IL-10）而不释放IL-12，并且只能驱动辅助性T（Th）2型T细胞。此外，非炎性MoDCs释放趋化因子，旨在招募Th2和调节性T细胞。相反，当MoDCs在Transwell共培养系统中与ECs和细菌一起孵育，并且可以通过受刺激的EC单层直接接触细菌时，它们会更具炎性，因为它们释放IL-12和IL-10，并诱导Th1和Th2反应。这些结果表明，ECs不仅仅是细菌经口进入的屏障，而且它们还积极影响DCs的激活特性。
