Compartmentalization of immune responses during staphylococcus aureus cranial bone flap infection

Joseph Cheatle, Amy Aldrich, William E Thorell, Michael D. Boska, Tammy L Kielian

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Decompressive craniectomy is often required after head trauma, stroke, or cranial bleeding to control subsequent brain swelling and prevent death. The infection rate after cranial bone flap replacement ranges from 0.8% to 15%, with an alarming frequency caused by methicillin-resistant Staphylococcus aureus, which is problematic because of recalcitrance to antibiotic therapy. Herein we report the establishment of a novel mouse model of S. aureus cranial bone flap infection that mimics several aspects of human disease. Bacteria colonized bone flaps for up to 4 months after infection, as revealed by scanning electron microscopy and quantitative culture, demonstrating the chronicity of the model. Analysis of a human cranial bone flap with confirmed S. aureus infection by scanning electron microscopy revealed similar structural attributes as the mouse model, demonstrating that it closely parallels structural facets of human disease. Inflammatory indices were most pronounced within the subcutaneous galeal compartment compared with the underlying brain parenchyma. Specifically, neutrophil influx and chemokine expression (CXCL2 and CCL5) were markedly elevated in the galea, which demonstrated substantial edema on magnetic resonance images, whereas the underlying brain parenchyma exhibited minimal involvement. Evaluation of immune mechanisms required for bacterial containment and inflammation revealed critical roles for MyD88-dependent signaling and neutrophils. This novel mouse model of cranial bone flap infection can be used to identify key immunologic and therapeutic mechanisms relevant to persistent bone flap infection in humans.

Original languageEnglish (US)
Pages (from-to)450-458
Number of pages9
JournalAmerican Journal of Pathology
Volume183
Issue number2
DOIs
StatePublished - Aug 1 2013

Fingerprint

Staphylococcus aureus
Bone and Bones
Infection
Electron Scanning Microscopy
Neutrophils
Decompressive Craniectomy
Chemokine CXCL2
Chemokine CCL5
Brain Edema
Brain
Methicillin-Resistant Staphylococcus aureus
Craniocerebral Trauma
Edema
Magnetic Resonance Spectroscopy
Stroke
Hemorrhage
Anti-Bacterial Agents
Inflammation
Bacteria
Therapeutics

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Compartmentalization of immune responses during staphylococcus aureus cranial bone flap infection. / Cheatle, Joseph; Aldrich, Amy; Thorell, William E; Boska, Michael D.; Kielian, Tammy L.

In: American Journal of Pathology, Vol. 183, No. 2, 01.08.2013, p. 450-458.

Research output: Contribution to journalArticle

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