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

ABSTRACT: Plasmacytoid dendritic cells (pDCs) detect microbial DNA via endosomal Toll-like receptor 9 (TLR9), yet the mechanisms by which they selectively internalize specific bacteria remain unclear. 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. BDCA2-Fc fusion proteins bound strongly to LAB, and glycan profiling revealed enrichment of Galβ1-3GalNAc-containing glycans in highly phagocytosed Lactococcus strains. These findings define BDCA2-dependent phagocytosis as a critical determinant of strain-specific LAB recognition by human pDCs and highlight the role of surface glycan composition in modulating innate immune sensing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE315830 | GEO | 2026/09/18

REPOSITORIES: GEO

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