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

Microbes Infect. 2011 Oct;13(11):914-22. doi: 10.1016/j.micinf.2011.05.004. Epub 2011 May 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Macrophages / immunology
  • Macrophages / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NADPH Oxidases / immunology*
  • NADPH Oxidases / metabolism
  • Nitric Oxide Synthase Type II / immunology*
  • Nitric Oxide Synthase Type II / metabolism
  • Pneumonia, Staphylococcal / immunology*
  • Rodent Diseases / immunology
  • Staphylococcus aureus / immunology*

Substances

  • Nitric Oxide Synthase Type II
  • NADPH Oxidases