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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE288378 | GEO | 2025/02/03

REPOSITORIES: GEO

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