Dendritic cells regulate the innate-adaptive balance in lymph nodes for optimal host defense

Lymph nodes (LNs) enable innate defense to limit pathogen dissemination while also driving adaptive immunity. Yet, certain innate responses can restrict adaptive processes, suggesting that these must be tightly regulated. Here, we report that after infection or immunization, LN architecture is rapidly altered, with large-scale, polarized recruitment of neutrophils and monocytes from inflamed blood vessels, and intranodal repositioning of NK cells. Mechanistically, dendritic cells (DCs) promote this process through expression of inflammatory chemokines and integrin ligands. While necessary for efficient pathogen containment, DC-driven innate cell responses paradoxically limit early adaptive immunity, with infiltrating neutrophils displacing lymphocytes and reducing the LN area available for T cell priming. Upon threat secession however, DCs and DC-recruited monocytes phagocytose the neutrophils, restoring tissue architecture and generating polarized domains for downstream adaptive immune cell activation. Thus, DCs orchestrate innate cell organization during inflammation, serving as rheostats of innate versus adaptive functions of the LN. RNA sequencing was performed to identify genes upregulated by DCs during early inflammation. Resident DC1s and DC2s were sorted from LNs at steady state as well as 6 hours post-CpG administration. We also performed intravascular staining with fluorescent anti-CD11c antibody to further sort on vasculature-associated and non-associated populations, to ask whether there were differences based on proximity to blood vessels.