Ligation of TLR9 on lymphoid progenitors promotes dendritic cell production at the expense of lymphopoiesis (83.11)

Abstract

Abstract Hematopoietic cells express TLR, raising the possibility that bacterial/viral products influence blood cell formation. We now show that common lymphoid progenitors (CLPs) express functional TLR9, and that dendritic cell production was strongly favored by TLR9 ligation with CpG ODN. TLR9 on CLPs rather than indirect cytokine mediated effects accounted for the shift in dendritic cell production, and CLPs became IL-7 unresponsive in culture. Similarly, CLPs from CpG treated mice had little ability to generate CD19+ cells and augmented competence to produce conventional (cDC), plasmacytoid (pDC) and interferon producing killer dendritic cells (IKDC) even in the absence of TNFα. Finally, lymphopoiesis in mice with active, but not latent HSV-1 infection was very similar to that seen in animals given CpG, and the changes were almost entirely mediated by TLR9. The findings bear on long standing controversies concerning the origins of dendritic cells and show how life-threatening infections may boost their production.