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Infection and Immunity, September 2006, p. 5058-5066, Vol. 74, No. 9
0019-9567/06/$08.00+0     doi:10.1128/IAI.01932-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Interplay of Pneumococcal Hydrogen Peroxide and Host-Derived Nitric Oxide

Olaf Hoffmann,^1, Janine Zweigner,^2,3, Shannon H. Smith,³ Dorette Freyer,¹ Cordula Mahrhofer,¹ Emilie Dagand,¹ Elaine I. Tuomanen,^3, and Joerg R. Weber^1,*

Department of Neurology,¹ Department of Microbiology and Hygiene, Charité—Universitaetsmedizin Berlin, Berlin, Germany,² Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee³

Received 25 November 2005/ Returned for modification 1 February 2006/ Accepted 7 June 2006

Reactive oxygen and nitrogen species are released by immune-competent cells and contribute to cellular damage. On the other hand, certain pathogens, including Streptococcus pneumoniae, are known to produce hydrogen peroxide (H₂O₂), while production of nitrogen radicals by bacteria presumably occurs but has been poorly studied. We determined the relative contributions of bacterial versus host-derived oxygen and nitrogen radicals to cellular damage in pneumococcal infection. A special focus was placed on peroxynitrite as a hypothetical common product formed by the reaction of H₂O₂ and NO. In microglial cultures, reduction of the formation of 3-nitrotyrosine and cellular damage required H₂O₂-deficient (spxB or carB) pneumococci and inhibition of host NO synthesis with aminoguanidine. In infected C57BL/6 mice, neuronal loss and immunopositivity for nitrotyrosine in the dentate gyrus were markedly reduced with spxB or carB bacterial mutants and in inducible nitric oxide synthase knockout mice. We conclude that although host and bacteria both produce oxygen and nitrogen radicals, the interplay of prokaryotic H₂O₂ and eukaryotic NO is a major contributor to cellular damage in pneumococcal meningitis.

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* Corresponding author. Mailing address: Department of Neurology, Charité—Universitaetsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Phone: 49 30 450 560192. Fax: 49 30 450 560942. E-mail: joerg.weber{at}charite.de.

Editor: J. N. Weiser

O.H. and J.Z. contributed equally to this paper.

E.I.T. and J.R.W. contributed equally to this paper.

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Infection and Immunity, September 2006, p. 5058-5066, Vol. 74, No. 9
0019-9567/06/$08.00+0     doi:10.1128/IAI.01932-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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