Potential role of human brain microvascular endothelial cells in the pathogenesis of brain abscess: Inhibition of Staphylococcus aureus by activation of indoleamine 2,3-dioxygenase

H. Schroten, B. Spors, C. Hucke, Monique Stins, Kwang Sik Kim, R. Adam, W. Däubener

Research output: Contribution to journalArticle

Abstract

Cerebral abscess is a rare complication of staphylococcal septicemia in infants associated with high mortality and morbidity. In the pathogenesis of abscess formation, S. aureus, one major causative agent, interacts with endothelial cells of the brain vessels before reaching the central nervous system. This study examined the growth of S. aureus in human brain microvascular endothelial cells (HBMEC) cultures stimulated with cytokines. IFN-γ inhibited S. aureus replication by the induction of indoleamine 2,3-dioxygenase (IDO) in HBMEC. This activation of IDO in HBMEC could be shown by RT-PCR and by detection of kynurenine in culture supernatants of activated cells. Resupplementation of L-tryptophan abrogated the inhibitory effect of IFN-γ on the growth of staphylococci, hence confirming the activation of indoleamine 2,3-dioxygenase as being responsible for the induced bacteriostasis. Addition of TNF-α enhanced the IFN-γ mediated antibacterial effects, whereas TNF-α alone had no influence on staphylococcal growth, Stimulation of HBMEC with IFN-γ failed to activate inducible nitric oxide synthase (iNOS) and subsequent production of nitric oxide (NO). Thus, intra- and extracellular depletion of L-tryptophan seems to be an important process in the defense against staphylococcal brain abscesses by means of creating an unfavorable microenvironment.

Original languageEnglish (US)
Pages (from-to)206-210
Number of pages5
JournalNeuropediatrics
Volume32
Issue number4
DOIs
StatePublished - 2001
Externally publishedYes

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Brain Abscess
Staphylococcus aureus
Endothelial Cells
Brain
Tryptophan
Growth
Kynurenine
Nitric Oxide Synthase Type II
Staphylococcus
Abscess
Sepsis
Nitric Oxide
Central Nervous System
Cell Culture Techniques
Cytokines
Morbidity
Polymerase Chain Reaction
Mortality

Keywords

  • HBMEC
  • IDO
  • IFN-γ
  • S. aureus
  • Tryptophan

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

Cite this

Potential role of human brain microvascular endothelial cells in the pathogenesis of brain abscess : Inhibition of Staphylococcus aureus by activation of indoleamine 2,3-dioxygenase. / Schroten, H.; Spors, B.; Hucke, C.; Stins, Monique; Kim, Kwang Sik; Adam, R.; Däubener, W.

In: Neuropediatrics, Vol. 32, No. 4, 2001, p. 206-210.

Research output: Contribution to journalArticle

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