Description
Group B streptococcus (GBS) is a Gram-positive bacterium that colonizes ∼25% of healthy adults but can be severely pathogenic in immune-compromised individuals such as newborns and the elderly. In fact, GBS infection is the leading cause of invasive disease in neonates and accounts for more than 5,000 cases of infection per year in Americans over 65 years of age. The ability of GBS to cross the blood-brain barrier (BBB) and cause meningitis is especially concerning because patient outcomes, even after recovery, can include severe neurological defects. Much research has been done on the interaction of GBS with the brain microvascular endothelial cells (BMECs) that line the capillaries of the brain and exhibit complex, tight junctions, which normally prevent foreign agents from passing into the nervous tissue. However, the response to GBS infection by astrocytes, whose endfeet cover the entire vasculature of the brain, has not been well characterized. Astrocytes are known to be important for controlling blood flow and in maintaining BBB function. We hypothesize that in response to GBS infection, astrocytes play a unique role in the development of inflammation and BBB breakdown. In this investigation, I examined the in vitro and in vivo interaction and response of astrocytes to GBS infection. Furthermore, I looked at the role that astrocytes play in BBB function during infection by utilizing an in vitro model of the BBB that included astrocytes and endothelial cells together in coculture.We found that, during infection, astrocytes react by upregulating the production of IL-6, IL-8, IL-1β, VEGF, MMP-2, and MMP-9. This shows that astrocytes are responding to GBS with inflammatory signals, growth signals , and BBB breakdown signals (MMP-2, MMP-9). With the coculture model, we also determined that astrocytes play both mitigating and detrimental roles during infection. We hope that these finding will help to further the understanding of the role of astrocytes during GBS infection and the progression of meningeal disease.
