Mast cells, histamine, and IL-6 regulate the selective influx of dendritic cell subsets into an inflamed lymph node

Abstract

In response to bacterial stimuli, multiple dendritic cell (DC) populations accumulate within the draining lymph node, thus enhancing opportunities for effective T cell-DC interaction. DC subpopulations, such as plasmacytoid, CD8(+), and CD11b(+) subsets, have distinct roles in determining the nature of the immune response. The mechanisms whereby individual DC subpopulations are mobilized and the extent to which these processes are linked to increases in overall lymph node cellularity have not been determined. In the current study, the mechanisms of DC subset mobilization to the draining auricular lymph node were examined after intradermal injection of Staphylococcus aureus-derived peptidoglycan. Using mast cell-deficient mice and local mast cell reconstitution, plasmacytoid and CD8(+) DC responses were shown to be mast cell dependent, whereas the CD11b(+) DC response was not. A histamine H2 receptor-dependent, CXCL9-independent pathway controlled the selective influx of both plasmacytoid and CD11b(+) DC into the lymph node, but not lymph node cellularity. In contrast, IL-6 was important for the mobilization of CD8(+) and CD11b(+) DC. TNF and IL-1 receptor were dispensable for plasmacytoid, CD11b(+), and CD8(+) DC responses. These findings provide novel opportunities for the selective mobilization of specific DC subsets to lymph nodes and demonstrate critical roles for both histamine and IL-6 in this process.