Bone marrow dendritic cell progenitors sense pathogens via toll-like receptors and subsequently migrate to inflamed lymph nodes

Abstract

Common dendritic cell progenitors (CDPs) in the bone marrow (BM) regenerate dendritic cells (DCs) in lymphoid and nonlymphoid tissues. How the dissemination of progenitor-derived DCs to peripheral tissues is regulated on need remains elusive. Microbes are sensed by pathogen recognition receptors such as Toll-like receptors (TLRs). We found that CDPs in the BM express TLR2, TLR4, and TLR9. On TLR stimulation, CDPs down-regulated CXCR4, the nonredundant chemokine receptor for their BM retention, up-regulated CCR7, and migrated to lymph nodes (LNs). When TLR agonists were injected locally, CDPs preferentially gave rise to DCs in inflamed LNs in expense of noninflamed LNs and the BM, but they did not alter their lineage differentiation and proliferative activity. Consequently, BM DC progenitors can sense TLR agonists and, via regulation of CXCR4 and CCR7, support the replenishment of DCs in reactive LNs. This mechanism likely developed to support DC homeostasis on specific need at sites of inflammation.