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Blood, 15 October 2005, Vol. 106, No. 8, pp. 2818-2826.
Prepublished online as a Blood First Edition Paper on July 19, 2005; DOI 10.1182/blood-2004-11-4321.


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IMMUNOBIOLOGY

Monocyte-derived dendritic cells activated by bacteria or by bacteria-stimulated epithelial cells are functionally different

Monica Rimoldi, Marcello Chieppa, Paola Larghi, Marisa Vulcano, Paola Allavena, and Maria Rescigno

From the Department of Experimental Oncology, European Institute of Oncology; Department of Immunology, Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy; and the Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.

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. (Blood. 2005;106:2818-2826)


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