GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE315nnn/GSE315830/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE315830GEOGSEfalseBDCA2 Dependent Phagocytosis Enables Strain Specific Activation of Human Plasmacytoid Dendritic Cells by Lactic Acid BacteriaPlasmacytoid 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.2026/09/18GSE315830GSM9438091GSM9438092GSM9438093GSM9438094GSM9438095GSM943809624676315830Homo sapiens