Streptococcus agalactiae pigment toxin induces a rapid non-canonical cell death in human dendritic cells
Abstract
Streptococcus agalactiae (Group B Streptococcus, GBS) is a major cause of neonatal sepsis and is increasingly associated with invasive infections in non-pregnant adults. GBS produces a cell wall-associated lipid toxin, the pigment (granadaene), a key virulence factor with cytotoxic and immunomodulatory properties. While its effects on several immune cells have been described, its impact on human dendritic cells remains largely unknown. Here, the role of the GBS pigment during infection of human monocyte-derived dendritic cells (moDCs) was assessed. Infection with pigmented GBS induced rapid cell death, characterized by early loss of mitochondrial membrane potential and phosphatidylserine exposure, culminating in membrane disruption. Inhibition of canonical cell death pathways indicated that moDC death occurs predominantly via a caspase-independent, mitochondria-driven mechanism, with caspase-8 activity enhancing the process. Blocking phagocytosis did not reduce cytotoxicity, whereas restriction of bacteria to the intracellular compartment markedly diminished cell death, indicating that the pigment primarily acts extracellularly. Following removal of extracellular bacteria and 24-h incubation, infected moDCs remained largely viable and exhibited comparable maturation and cytokine responses, regardless of whether the infecting bacteria expressed the pigment. Together, these findings indicate that pigment-dependent cytotoxicity in moDC infections is mediated by extracellular GBS.
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BibTeX
@article{riegner2026streptococcus,
title = {{Streptococcus agalactiae pigment toxin induces a rapid non-canonical cell death in human dendritic cells}},
author = {Anna Riegner and Emily Friedrich and Lea A. Tölken and Nikolai Siemens},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-73932-7},
url = {https://www.nature.com/articles/s41598-026-73932-7},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Streptococcus agalactiae pigment toxin induces a rapid non-canonical cell death in human dendritic cells
AU - Anna Riegner
AU - Emily Friedrich
AU - Lea A. Tölken
AU - Nikolai Siemens
PY - 2026
DA - 2026/10/02
JO - Scientific Reports
DO - 10.1038/s41598-026-73932-7
UR - https://www.nature.com/articles/s41598-026-73932-7
AB - Streptococcus agalactiae (Group B Streptococcus, GBS) is a major cause of neonatal sepsis and is increasingly associated with invasive infections in non-pregnant adults. GBS produces a cell wall-associated lipid toxin, the pigment (granadaene), a key virulence factor with cytotoxic and immunomodulatory properties. While its effects on several immune cells have been described, its impact on human dendritic cells remains largely unknown. Here, the role of the GBS pigment during infection of human monocyte-derived dendritic cells (moDCs) was assessed. Infection with pigmented GBS induced rapid cell death, characterized by early loss of mitochondrial membrane potential and phosphatidylserine exposure, culminating in membrane disruption. Inhibition of canonical cell death pathways indicated that moDC death occurs predominantly via a caspase-independent, mitochondria-driven mechanism, with caspase-8 activity enhancing the process. Blocking phagocytosis did not reduce cytotoxicity, whereas restriction of bacteria to the intracellular compartment markedly diminished cell death, indicating that the pigment primarily acts extracellularly. Following removal of extracellular bacteria and 24-h incubation, infected moDCs remained largely viable and exhibited comparable maturation and cytokine responses, regardless of whether the infecting bacteria expressed the pigment. Together, these findings indicate that pigment-dependent cytotoxicity in moDC infections is mediated by extracellular GBS.
SN - 2045-2322
ER -