PMID- 16030185 OWN - NLM STAT- MEDLINE DCOM- 20051107 LR - 20210206 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 106 IP - 8 DP - 2005 Oct 15 TI - Monocyte-derived dendritic cells activated by bacteria or by bacteria-stimulated epithelial cells are functionally different. PG - 2818-26 AB - 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. FAU - Rimoldi, Monica AU - Rimoldi M AD - Department of Experimental Oncology, European Institute of Oncology, Istituto di Ricerche Farmacologiche, Mario Negri, Milan, Italy. FAU - Chieppa, Marcello AU - Chieppa M FAU - Larghi, Paola AU - Larghi P FAU - Vulcano, Marisa AU - Vulcano M FAU - Allavena, Paola AU - Allavena P FAU - Rescigno, Maria AU - Rescigno M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050719 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (CCL20 protein, mouse) RN - 0 (Chemokine CCL20) RN - 0 (Chemokines, CC) RN - 0 (Macrophage Inflammatory Proteins) RN - 130068-27-8 (Interleukin-10) RN - 187348-17-0 (Interleukin-12) SB - IM MH - Animals MH - *Cell Differentiation MH - Cells, Cultured MH - Chemokine CCL20 MH - Chemokines, CC/metabolism MH - Dendritic Cells/*cytology/*immunology/metabolism MH - Epithelial Cells/cytology/*immunology/metabolism/*microbiology MH - Flagella/physiology MH - Gram-Positive Bacteria/cytology/pathogenicity/*physiology MH - Humans MH - Interleukin-10/metabolism MH - Interleukin-12/metabolism MH - Macrophage Inflammatory Proteins/metabolism MH - Mice MH - Monocytes/*cytology/immunology/metabolism MH - Th1 Cells/immunology MH - Th2 Cells/immunology EDAT- 2005/07/21 09:00 MHDA- 2005/11/08 09:00 CRDT- 2005/07/21 09:00 PHST- 2005/07/21 09:00 [pubmed] PHST- 2005/11/08 09:00 [medline] PHST- 2005/07/21 09:00 [entrez] AID - S0006-4971(20)69125-X [pii] AID - 10.1182/blood-2004-11-4321 [doi] PST - ppublish SO - Blood. 2005 Oct 15;106(8):2818-26. doi: 10.1182/blood-2004-11-4321. Epub 2005 Jul 19.