NADPH-oxidase but not inducible nitric oxide synthase contributes to resistance in a murine Staphylococcus aureus Newman pneumonia model.

J. Kohler, K. Breitbach, C. Renner, A. K. Heitsch, A. Bast, N. van Rooijen, S. Vogelgesang, I. Steinmetz

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Staphylococcus aureus is a pathogen that often causes severe nosocomial infections including pneumonia. The present study was designed to examine innate phagocyte mediated immune mechanisms using a previously described murine S. aureus Newman pneumonia model. We found that BALB/c mice represent a more susceptible mouse strain compared to C57BL/6 mice after intranasal S. aureus Newman challenge. Depletion experiments revealed that neutrophils are a crucial determinant for resistance whereas depletion of alveolar macrophages protected mice to some degree from acute pulmonary S. aureus challenge. C57BL/6 mice lacking the subunit gp91phox of the NADPH-oxidase (gp91phox-/- mice) proved to be highly susceptible against the pathogen. In contrast, C57BL/6 inducible nitric oxidase synthase deficient (iNOS-/-) mice did not differ in their clinical outcome after infection. Neither bone marrow macrophages from iNOS-/- nor from gp91phox-/- mice were impaired in controlling intracellular persistence of S. aureus. Our data suggest that neutrophil and NADPH-oxidase mediated mechanisms are essential components in protecting the host against pulmonary S. aureus Newman challenge. On contrary, macrophages as well as NO mediated mechanisms do not seem to play a critical role for resistance in this model.
Original languageEnglish
Pages (from-to)914-922
Number of pages9
JournalMicrobes and Infection
Volume13
Issue number11
DOIs
Publication statusPublished - Oct 2011

Keywords

  • Staphylococcus aureus
  • Macrophage
  • Neutrophil
  • Nitric oxide
  • NADPH-oxidase
  • ALVEOLAR MACROPHAGES
  • SEPTIC ARTHRITIS
  • LIPOTEICHOIC ACID
  • PROTECTIVE ROLE
  • HOST-DEFENSE
  • MOUSE MODEL
  • INFECTION
  • MICE
  • NEUTROPHILS
  • DEPLETION

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