Biofilm-infected intracerebroventricular shunts elicit inflammation within the central nervous system

Jessica Snowden, Matt Beaver, Mark S. Smeltzer, Tammy L Kielian

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Central nervous system catheter infections are a serious complication in the treatment of hydrocephalus. These infections are commonly caused by Staphylococcus epidermidis and Staphylococcus aureus, both known to form biofilms on the catheter surface. Our objective was to generate a novel murine model of central nervous system catheter-associated biofilm infection using a clinical S. aureus isolate and characterize the nature of the inflammatory response during biofilm growth. Silicone catheters were precoated with S. aureus to facilitate bacterial attachment, whereupon infected or sterile catheters were stereotactically inserted into the lateral ventricle of the brain in C57BL/6 mice and evaluated at regular intervals through day 21 postinsertion. Animals tolerated the procedure well, with no clinical signs of illness or bacterial growth seen in the control group. Bacterial titers associated with central nervous system catheters were significantly elevated compared to those from the surrounding parenchyma, consistent with biofilm formation and minimal planktonic spread of infection. Catheter-associated bacterial burdens progressively increased, with maximal colonization achieved at day 7 postinfection. Analysis of inflammatory infiltrates by fluorescence-activated cell sorting (FACS) revealed significant macrophage and neutrophil influx, which peaked at days 3 and 5 to 7, respectively. In contrast, there were no detectable immune infiltrates associated with tissues surrounding sterile catheters. Biofilm infection led to significant increases in chemokine (CXCL1 and CCL2) and proinflammatory cytokine (interleukin 17 [IL-17]) expression in tissues surrounding infected central nervous system catheters. Based on these results, we propose this approach is a valid animal model for further investigations of catheter-associated central nervous system shunt infections.

Original languageEnglish (US)
Pages (from-to)3206-3214
Number of pages9
JournalInfection and immunity
Volume80
Issue number9
DOIs
StatePublished - Sep 1 2012

Fingerprint

Biofilms
Catheters
Central Nervous System
Inflammation
Staphylococcus aureus
Central Nervous System Infections
Chemokine CXCL1
Infection
Catheter-Related Infections
Staphylococcus epidermidis
Interleukin-17
Chemokine CCL2
Lateral Ventricles
Silicones
Hydrocephalus
Growth
Inbred C57BL Mouse
Flow Cytometry
Neutrophils
Animal Models

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Biofilm-infected intracerebroventricular shunts elicit inflammation within the central nervous system. / Snowden, Jessica; Beaver, Matt; Smeltzer, Mark S.; Kielian, Tammy L.

In: Infection and immunity, Vol. 80, No. 9, 01.09.2012, p. 3206-3214.

Research output: Contribution to journalArticle

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