The study of monocyte-derived DCs in vivo has been hampered owing to a lack of specific markers, but the authors found that DCs generated from mouse monocytes in vitro could be distinguished from classical DCs by their unique expression of DC-specific ICAM3-grabbing non-integrin (DC-SIGN; also known as CD209). DC-SIGN+ cells were detected in peripheral lymph nodes of mice that were challenged systemically with LPS or Gram-negative bacteria, but were not observed in the lymph nodes following challenge with other TLR ligands or with bacteria that did not express LPS. The LPS-induced DC-SIGN+ cells localized to the T cell zone of lymph nodes and were found to be distinct from classical DCs, macrophages and monocytes. However, the DC-SIGN+ cells could not be detected in LPS-treated TLR4-deficient mice, confirming the requirement of TLR4 for mobilization of this population.
By transferring bone marrow-derived monocytes into congenic mice, the authors confirmed that the LPS-induced DC-SIGN+ cells were of monocytic origin. Furthermore, DC-SIGN+ cells were not mobilized to the lymph nodes of LPS-treated mice if monocytes were conditionally depleted, but were recruited normally in FMS-related tyrosine kinase 3 (FLT3)-deficient mice, which lack classical DCs. The monocyte-derived DC-SIGN+ cells were shown to require expression of L-selectin and CC-chemokine receptor 7 (CCR7) to enter lymph nodes, suggesting that these cells are recruited directly from the blood. Furthermore, in functional assays, purified monocyte-derived DC-SIGN+ cells were at least as good as, and often better than, classical lymph node DCs at capturing antigen and presenting it to T cells. Remarkably, the DC-SIGN+ cells activated both CD4+ and CD8+ T cells in an antigen-specific manner and could cross-present antigens associated with Gram-negative bacteria as effectively as classical DEC205+ DCs.
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