CXC chemokine receptor-2 ligands are required for neutrophil-mediated host defense in experimental brain abscesses

T. Kielian, B. Barry, W. F. Hickey

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

We have developed a mouse brain abscess model by using Staphylococcus aureus, one of the main etiologic agents of brain abscesses in humans. Direct damage to the blood-brain barrier was observed from 24 h to 7 days after S. aureus exposure as demonstrated by the accumulation of serum IgG in the brain parenchyma. Evaluation of brain abscesses by immunohistochemistry and flow cytometry revealed a prominent neutrophil infiltrate. To address the importance of neutrophils in the early containment of S. aureus infection in the brain, mice were transiently depleted of neutrophils before implantation of bacteria-laden beads. Neutrophil-depleted animals consistently demonstrated more severe brain abscesses and higher CNS bacterial burdens compared with control animals. S. aureus led to the induction of numerous chemokines in the brain, including macrophage-inflammatory protein (MIP)-1α/CCL3, MIP-1β/CCL4, MIP-2/CXCL1, monocyte chemoattractant protein-1/CCL2, and TCA-3/ CCL1, within 6 h after bacterial exposure. These chemokines also were expressed by both primary cultures of neonatal mouse microglia and astrocytes exposed to heat-inactivated S. aureus in vitro. Because neutrophils constitute the majority of the cellular infiltrate in early brain abscess development, subsequent analysis focused on MIP-2 and KC/CXCL1, two neutrophil-attracting CXC chemokines. Both MIP-2 and KC protein levels were significantly elevated in the brain after S. aureus exposure. Neutrophil extravasation into the brain parenchyma was impaired in CXCR2 knockout mice and was associated with increased bacterial burdens. These studies demonstrate the importance of the CXCR2 ligands MIP-2 and KC and neutrophils in the acute host response to S. aureus in the brain.

Original languageEnglish (US)
Pages (from-to)4634-4643
Number of pages10
JournalJournal of Immunology
Volume166
Issue number7
DOIs
StatePublished - Apr 1 2001

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Interleukin-8B Receptors
Brain Abscess
Neutrophils
Staphylococcus aureus
Chemokine CXCL2
Ligands
Brain
Macrophage Inflammatory Proteins
Chemokines
CXC Chemokines
Chemokine CCL2
Microglia
Blood-Brain Barrier
Knockout Mice
Astrocytes
Flow Cytometry
Immunoglobulin G
Hot Temperature
Immunohistochemistry
Bacteria

ASJC Scopus subject areas

  • Immunology

Cite this

CXC chemokine receptor-2 ligands are required for neutrophil-mediated host defense in experimental brain abscesses. / Kielian, T.; Barry, B.; Hickey, W. F.

In: Journal of Immunology, Vol. 166, No. 7, 01.04.2001, p. 4634-4643.

Research output: Contribution to journalArticle

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