BDCA2 Dependent Phagocytosis Enables Strain Specific Activation of Human Plasmacytoid Dendritic Cells by Lactic Acid Bacteria

We demonstrate that type I interferon (IFN-I) responses to lactic acid bacteria (LAB) are entirely dependent on phagocytosis and exhibit pronounced strain specificity. Among tested strains, Lactococcus lactis strain Plasma (LC-Plasma) was efficiently phagocytosed and potently induced IFN-α in both primary human pDCs and CAL-1 cells, whereas closely related strains showed minimal uptake and cytokine production.

Phagocytosis was essential for CD40 and CD86 upregulation as well as TLR9-dependent IFN-α secretion. Transcriptomic and functional analyses identified BDCA2, a galactose-binding C-type lectin receptor, as a key mediator of LAB uptake. Blocking BDCA2 significantly impaired both phagocytosis and cytokine responses.