Blood-derived inflammatory dendritic cells in lymph nodes stimulate acute T helper type 1 immune responses

Abstract

Lymphocytes are typically recruited into lymph nodes via CCR7. Gunn and colleagues identify an 'inflammatory DC' subset that is recruited directly from the bloodstream through the use of CCR2 and that induces potent T helper type 1 priming. T helper type 1 (TH1)-polarized immune responses, which confer protection against intracellular pathogens, are thought to be initiated by dendritic cells (DCs) that enter lymph nodes from peripheral tissues. Here we found after viral infection or immunization, inflammatory monocytes were recruited into lymph nodes directly from the blood to become CD11c+CD11bhiGr-1+ inflammatory DCs, which produced abundant interleukin 12p70 and potently stimulated TH1 responses. This monocyte extravasation required the chemokine receptor CCR2 but not the chemokine CCL2 or receptor CCR7. Thus, the accumulation of inflammatory DCs and TH1 responses were much lower in Ccr2−/− mice, were preserved in Ccl2−/− mice and were relatively higher in CCL19–CCL21-Ser–deficient plt mutant mice, in which all other lymph node DC types were fewer in number. We conclude that blood-derived inflammatory DCs are important in the development of TH1 immune responses.