title: NADPH-oxidase but not inducible nitric oxide synthase contributes to resistance in a murine Staphylococcus aureus Newman pneumonia model.
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.
authors.affiliation: Friedrich Loeffler Institute of Medical Microbiology, Ernst Moritz Arndt University Greifswald, Martin-Luther Str. 6, 17489 Greifswald, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Köhler
authors.forename: Katrin
authors.initials: K
authors.lastname: Breitbach
authors.forename: Cäcilia
authors.initials: C
authors.lastname: Renner
authors.forename: Anne-Katrin
authors.initials: AK
authors.lastname: Heitsch
authors.forename: Antje
authors.initials: A
authors.lastname: Bast
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Silke
authors.initials: S
authors.lastname: Vogelgesang
authors.forename: Ivo
authors.initials: I
authors.lastname: Steinmetz
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000276:immunology* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000276:immunology* / Q000378:metabolism; D011023:Pneumonia, Staphylococcal / Q000276:immunology*; D012376:Rodent Diseases / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology*
chemical_list: D052247:Nitric Oxide Synthase Type II; D019255:NADPH Oxidases