gms | German Medical Science

Objective: A relationship between postoperative infections and a prolonged survival in glioblastoma patients still remains controversial. The pathogens most frequently detected in this context are Staphylococcus species. Although the interaction of S. aureus with different human cell types was investigated before, no data about infection of glioblastoma cells and astrocytes is known. The main objective of this study was to investigate the course of S. aureus infection of glioblastoma cells (GBM) and human brain astrocytes (HBA). Therefore, we established an in vitro infection model.

Methods: Four different GBM cell cultures and one HBA cell culture were infected with two wild-type strains of S. aureus (6850, LS1) with a MOI of 10. After 90 min the percentage of ingested bacteria was determined. In a persistence assay, the survival of intracellular bacteria was investigated after 2, 4, and 7 days post infection. At the same time points cell death of the human cells was examined. Changes in secretion of IL-6 and IL-8 were measured by ELISA.

Results: S. aureus was able to infect GBM as well as HBA cells. The cells ingested between 0.1% and 4.7% of the bacteria. After ingestion the bacteria induced cell death in about 28.5% of the host cells. The remaining human cells eliminated the bacteria very quickly; and the human cells recovered. In addition, the intracellular bacteria presented a high population of small colony variants (SCVs) which are associated with host immune response evasion. On day 4, 13.2% (6850) and 1.7% (LS1) of the intracellular bacteria were left in the GBM cells, of which 10.3% and 31.3% were SCVs. In the HBA cells 0.6% (6850) and 4.7% (LS1) bacteria were left, with 10.1% and 15.3% SCVs. The differences in the elimination of the bacteria between GBM cells and HBA and the phenotype switch during the course of infection were statistically significant for both S. aureus strains. The infected GBM cells and HBA became activated and secreted cytokines. There was a significant increase in secretion of IL-6 (6850: 109fold, LS1: 1001fold) and IL-8 (6850: 339fold, LS1: 488fold) 24h after infection, compared with the uninfected cells

Conclusion: Our data show for the first time, that S. aureus is able to infect glioblastoma cells as well as astrocytes cells. Moreover, the GBM cells were more susceptible to bacterial infection than the HBA cells. The inducible secretion of proinflammatory cytokines may lead to an enhanced antitumor immunity in GBM.