Background: Shunt infection is a common complication in the treatment of hydrocephalus in children. The immunologic mechanisms that shape the inflammatory response and bacterial control are not well defined. MyD88 is an important immune adaptor molecule that has been shown to play a role in regulating inflammation but not bacterial burdens in brain abscess. However, it has not been studied in the setting of shunt infection. In vitro studies suggest that human neonates have attenuated MyD88-dependent responses, which may explain their increased risk of shunt infection. In this study, we evaluate the role of MyD88 in S. epidermidis shunt infection.
Methods: S. epidermidis coated catheters were stereotactically implanted into the lateral ventricle of 8 week old wild type (WT) or MyD88 knock out (KO) mice. Catheters and the surrounding brain parenchyma were cultured with quantification of bacteria via serial dilution at days 1 and 3 post-implantation. Clinical signs of illness and weight loss were also documented daily. Chemokine and cytokine levels in the brain tissue surrounding the catheter were measured via multiplex.
Results: MyD88 KO mice had increased weight loss and clinical illness scores at all time points post-infection. No mortality was observed in either group. Bacterial cultures (Figure) revealed an increase in total bacterial burdens as well as an increase in parenchymal spread of bacteria from the catheter in the MyD88 KO mice in comparison to wild type mice. Pro-inflammatory chemokines and cytokines MIP2, IL-6, MCP-1 and CXCL1 were increased in MyD88 KO mice, particularly at day 1 following implantation. There was no difference in IL-1βor IL-10 levels in WT versus MyD88 KO mice.
Conclusion: MyD88 plays a role in the early control of bacterial infection in S. epidermidis shunt infection. The increased parenchymal spread of bacteria from the catheter is similar to the phenotype observed in our infant infection model, suggesting that alterations in MyD88 signaling in young mice may play a role in the increased planktonic spread of S. epidermidis. These results suggest that MyD88 plays an important role in regulating the inflammatory response to infection, particularly initial responses and bacterial burdens.
J. Snowden, None