Monocyte-derived dendritic cells activated by bacteria or by bacteria-stimulated epithelial cells are functionally different.
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.
Rimoldi
Monica
M
Department of Experimental Oncology, European Institute of Oncology, Istituto di Ricerche Farmacologiche, Mario Negri, Milan, Italy.
Chieppa
Marcello
M
Larghi
Paola
P
Vulcano
Marisa
M
Allavena
Paola
P
Rescigno
Maria
M
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D005407:Flagella / Q000502:physiology; D006094:Gram-Positive Bacteria / Q000166:cytology / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
C493447:CCL20 protein, mouse; D054418:Chemokine CCL20; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D016753:Interleukin-10; D018664:Interleukin-12