IL-10 plays an important role in the control of inflammation but not in the bacterial burden in S. epidermidis CNS catheter infection

Abstract

BackgroundShunt infection is a frequent and serious complication in the surgical treatment in hydrocephalus. Previous studies have shown an attenuated immune response to these biofilm-mediated infections. We proposed that IL-10 reduces the inflammatory response to Staphylococcus epidermidis (S. epidermidis) CNS catheter infection.MethodsIn this study, a murine model of catheter-associated S. epidermidis biofilm infection in the CNS was generated based on a well-established similar model for S. aureus. The catheters were pre-coated with a clinically derived biofilm-forming strain of S. epidermidis (strain 1457) which were then stereotactically implanted into the lateral left ventricle of 8-week-old C57BL/6 and IL-10 knockout (IL-10 knockout) mice. Bacterial titers as well as cytokine and chemokine levels were measured at days 3, 5, 7, and 10 in mice implanted with sterile and S. epidermidis-coated catheters.ResultsCultures demonstrated a catheter-associated and parenchymal infection that persisted through 10 days following infection. Cytokine analysis of the tissue surrounding the catheters revealed greater levels of IL-10, an anti-inflammatory cytokine, in the infected group compared to the sterile. In IL-10 KO mice, we noted no change in bacterial burdens, showing that IL-10 is not needed to control the infection in a CNS catheter infection model. However, IL-10 KO mice had increased levels of pro-inflammatory mediators in the tissues immediately adjacent to the infected catheter, as well as an increase in weight loss.ConclusionsTogether our results indicate that IL-10 plays a key role in regulating the inflammatory response to CNS catheter infection but not in control of bacterial burdens. Therefore, IL-10 may be a useful therapeutic target for immune modulation in CNS catheter infection but this should be used in conjunction with antibiotic therapy for bacterial eradication.

Pathogenic Mechanisms and Host Interactions in Staphylococcus epidermidis Device-Related Infection

“…In a S. epidermidis DRI mouse model it was shown that IL-10 was involved in reducing infection-associated morbidity, with higher levels of pro-inflammatory cytokines and greater weight loss in IL-10 KO animals. Interestingly, bacterial counts were the same in both wild-type and KO strains, suggesting that IL-10 does not impact bacterial clearance (Gutierrez-Murgas et al, 2016 ). Overall, despite differences due to different S. epidermidis strains and its effect in different tissues, it can be hypothesized that lower induction of pro-inflammatory cytokines together with high IL-10 production, can contribute to the sub-acute nature of S. epidermidis infections.…”

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“…Regulatory T cells (Treg cells), known as suppressor T cells, are subpopulation of T cells and modulate the immune systems (Kikodze, Pantsulaia, & Chikovani, 2016). IL-10 is one of the Treg cells and known as a key regulator of immunity to many infection or inflammatory disease (Gutierrez-Murgas, Gwenn, Danielle, Matthew, & Jessica, 2016). For instance, high levels of IL-10 gene expressions have protective effect against malaria parasites infection (Niikura, Inoue, & Kobayashi, 2011).…”

Unexpected eosinophilia in children affected by hydrocephalus accompanied with shunt infection

“…Immunological models seeking to elucidate the immune reaction to Staphylococcus epidermidis or Staphylococcus aureus infections are based on animal models. It is uncertain whether animal models fully depicted the corresponding reactions in humans [ 7 ]. Furthermore, some experimental work on animals points to non-compatibility of the immunological reaction between different races of rodents [ 24 ].…”