BDCA2-dependent phagocytosis enables strain-specific activation of 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 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. Glycan profiling identified glycan signatures associated with highly phagocytosed Lactococcus strains. These findings define BDCA2-dependent phagocytosis as a critical determinant of strain-specific LAB recognition by human pDCs.
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BibTeX
@article{hori2026bdca2dependent,
title = {{BDCA2-dependent phagocytosis enables strain-specific activation of plasmacytoid dendritic cells by lactic acid bacteria}},
author = {Shota Hori and Yu Hirose and Julia Matsuo-Dapaah and Jiawen Zheng and Toshikazu Tsuji and Hirotaka Fujita and Muneaki Nanao and Ryohei Tsuji},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.118033},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03416-4},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - BDCA2-dependent phagocytosis enables strain-specific activation of plasmacytoid dendritic cells by lactic acid bacteria
AU - Shota Hori
AU - Yu Hirose
AU - Julia Matsuo-Dapaah
AU - Jiawen Zheng
AU - Toshikazu Tsuji
AU - Hirotaka Fujita
AU - Muneaki Nanao
AU - Ryohei Tsuji
PY - 2026
DA - 2026/10/23
JO - iScience
DO - 10.1016/j.isci.2026.118033
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03416-4
AB - 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 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. Glycan profiling identified glycan signatures associated with highly phagocytosed Lactococcus strains. These findings define BDCA2-dependent phagocytosis as a critical determinant of strain-specific LAB recognition by human pDCs.
SN - 2589-0042
ER -