Related Experiment Video
Updated: Apr 25, 2026
A Murine Model of Group B Streptococcus Vaginal Colonization
Published on: November 16, 2016
Macrophage induced gelsolin in response to Group B Streptococcus (GBS) infection
Katia Fettucciari1, Pamela Ponsini, Camilla Palumbo
1Department of Experimental Medicine, Perugia University, Perugia, Italy.
Abstract:
Group B Streptococcus (GBS) has evolved several strategies to avoid host defences. We have shown that interaction of macrophages with GBS causes macrophage calpain activation, cytoskeletal disruption and apoptosis, consequences of intracellular calcium increase induced by membrane permeability alterations provoked by GBS-β-haemolysin. Open question remains about what effect calcium influx has on other calcium-sensing proteins such as gelsolin, involved in cytoskeleton modulation and apoptosis. Therefore we analysed the effect of GBS-III-COH31:macrophage interaction on gelsolin expression. Here we demonstrate that an early macrophage response to GBS-III-COH31 is a very strong gelsolin increase, which occurs in a time- and infection-ratio-dependent manner. This is not due to transcriptional events, translation events, protein turnover alterations, or protein-kinase activation, but to calcium influx, calpain activation and caspase-3 degradation. In fact, EGTA and PD150606 (calpain inhibitor) prevented gelsolin increase while BAF (caspase inhibitor) enhanced it. Since gelsolin increase is induced by highly β-haemolytic GBS-III-NEM316 and GBS-V-10/84, but not by weakly β-haemolytic GBS, or GBS-III-COH31 in conditions suppressing β-haemolysin expression/activity and the presence of dipalmitoylphosphatidylcholine (β-haemolysin inhibitor), GBS-β-haemolysin is solely responsible for gelsolin increase causing, through membrane permeability defects, calcium influx and calpain activation. Early gelsolin increase could represent a macrophage response to antagonize apoptosis since gelsolin knockdown increases macrophage susceptibility to GBS-induced apoptosis. This response seems to be GBS specific because macrophage apoptosis by Staurosporine or Cycloeximide does not induce gelsolin.
Insights
Group B Streptococcus (GBS) infection increases gelsolin in macrophages via calcium influx and calpain activation, mediated by GBS-β-haemolysin. This early gelsolin response may help prevent GBS-induced macrophage apoptosis.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Group B Streptococcus (GBS) employs strategies to evade host immune defenses.
- GBS interaction with macrophages triggers calpain activation, cytoskeletal disruption, and apoptosis.
- GBS-induced intracellular calcium increase, via membrane permeability alterations by GBS-β-haemolysin, is a key factor.
Purpose of the Study:
- To investigate the effect of GBS interaction on gelsolin expression in macrophages.
- To elucidate the role of calcium influx and calpain activation in GBS-induced gelsolin modulation.
- To determine the specific GBS virulence factor responsible for gelsolin upregulation.
Main Methods:
- Macrophage-GBS interaction analysis.
- Gelsolin expression quantification.
- Inhibition studies using EGTA, PD150606 (calpain inhibitor), and BAF (caspase inhibitor).
- Assessment of GBS strains with varying β-haemolytic activity and use of β-haemolysin inhibitors.
Main Results:
- Macrophage interaction with GBS-III-COH31 induced a significant increase in gelsolin expression.
- Gelsolin upregulation was dependent on calcium influx, calpain activation, and caspase-3 degradation, not transcriptional or translational changes.
- GBS-β-haemolysin was identified as the sole GBS factor responsible for inducing gelsolin increase.
- Gelsolin knockdown enhanced macrophage susceptibility to GBS-induced apoptosis, suggesting a protective role.
Conclusions:
- GBS-β-haemolysin triggers gelsolin increase in macrophages through membrane permeability defects, calcium influx, and calpain activation.
- Early gelsolin upregulation serves as a macrophage defense mechanism to counteract GBS-induced apoptosis.
- This gelsolin response is specific to GBS infection and not observed with other apoptotic stimuli.
