TY - JOUR
T1 - IL-10 plays an important role in the control of inflammation but not in the bacterial burden in S. epidermidis CNS catheter infection
AU - Gutierrez-Murgas, Yenis M.
AU - Skar, Gwenn
AU - Ramirez, Danielle
AU - Beaver, Matthew
AU - Snowden, Jessica
N1 - Funding Information:
This work was funded by the Fullbright-Cerrejon Scholarship to YGM and the Cheryl Ann Lozier Memorial Research Fund, Edna Ittner Pediatric Research Support Fund, and the National Institute of Neurologic Disorders and Stroke (1K08NS069812, 1R01NS092732) to JNS. Additional support is provided by the University of Nebraska Medical Center Departments of Pediatrics and Pathology/Microbiology.
Publisher Copyright:
© 2016 The Author(s).
PY - 2016/10/13
Y1 - 2016/10/13
N2 - Background: Shunt 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. Methods: In 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. Results: Cultures 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. Conclusions: Together 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.
AB - Background: Shunt 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. Methods: In 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. Results: Cultures 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. Conclusions: Together 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.
KW - Biofilm
KW - Catheter
KW - Central nervous system
KW - Chemokines
KW - Cytokines
KW - IL-10
KW - S. epidermidis
KW - Shunt
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U2 - 10.1186/s12974-016-0741-1
DO - 10.1186/s12974-016-0741-1
M3 - Article
C2 - 27737696
AN - SCOPUS:84992051985
SN - 1742-2094
VL - 13
JO - Journal of Neuroinflammation
JF - Journal of Neuroinflammation
IS - 1
M1 - 271
ER -