What is it about?
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.
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Why is it important?
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.
Perspectives
This study demonstrates for the first time that an early MΦ response to the β-haemolytic strains of GBS (GBS-III-COH31, GBS-III-NEM316 and GBS-V-10/84) is a marked early gelsolin increase, mediated by an influx of extracellular Ca2+, calpain activation and consequent caspase-3 degradation without involvement of transcriptional and translation events or protein turnover alterations. The response is highly dependent on the expression level of β-haemolytic activity and plays an anti-apoptotic role but also appears to contribute to controlling phagocytosis and cytoskeleton dynamics in the early phase of infection
Dr Katia Fettucciari
University of Perugia
Read the Original
This page is a summary of: Macrophage induced gelsolin in response to Group BStreptococcus(GBS) infection, Cellular Microbiology, September 2014, Wiley,
DOI: 10.1111/cmi.12338.
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