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Infection and Immunity, December 2008, p. 5862-5872, Vol. 76, No. 12
0019-9567/08/$08.00+0     doi:10.1128/IAI.00865-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Staphylococcus aureus Elicits Marked Alterations in the Airway Proteome during Early Pneumonia{triangledown} ,{ddagger}

Christy L. Ventura,1,6,10,{dagger} Roger Higdon,2,3 Laura Hohmann,4 Daniel Martin,4,5 Eugene Kolker,2,3,7 H. Denny Liggitt,8 Shawn J. Skerrett,9 and Craig E. Rubens1,6*

Division of Infectious Diseases, Center for Childhood Infections and Prematurity Research,1 Center for Developmental Therapeutics, Seattle Children's Hospital Research Institute,2 BIATECH Institute,3 Institute for Systems Biology,4 Fred Hutchinson Cancer Research Center,5 Departments of Pediatrics,6 Medical Education and Biomedical Informatics,7 Comparative Medicine,8 Medicine, University of Washington School of Medicine, Seattle, Washington,9 Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana,10

Received 14 July 2008/ Returned for modification 5 August 2008/ Accepted 3 October 2008

Pneumonia caused by Staphylococcus aureus is a growing concern in the health care community. We hypothesized that characterization of the early innate immune response to bacteria in the lungs would provide insight into the mechanisms used by the host to protect itself from infection. An adult mouse model of Staphylococcus aureus pneumonia was utilized to define the early events in the innate immune response and to assess the changes in the airway proteome during the first 6 h of pneumonia. S. aureus actively replicated in the lungs of mice inoculated intranasally under anesthesia to cause significant morbidity and mortality. By 6 h postinoculation, the release of proinflammatory cytokines caused effective recruitment of neutrophils to the airway. Neutrophil influx, loss of alveolar architecture, and consolidated pneumonia were observed histologically 6 h postinoculation. Bronchoalveolar lavage fluids from mice inoculated with phosphate-buffered saline (PBS) or S. aureus were depleted of overabundant proteins and subjected to strong cation exchange fractionation followed by liquid chromatography and tandem mass spectrometry to identify the proteins present in the airway. No significant changes in response to PBS inoculation or 30 min following S. aureus inoculation were observed. However, a dramatic increase in extracellular proteins was observed 6 h postinoculation with S. aureus, with the increase dominated by inflammatory and coagulation proteins. The data presented here provide a comprehensive evaluation of the rapid and vigorous innate immune response mounted in the host airway during the earliest stages of S. aureus pneumonia.

* Corresponding author. Present address: Seattle Children's Hospital, Metropolitan Park West Bldg., 1100 Olive Way, M/S MPW10, Seattle, WA 98101. Phone: (206) 884-2777. Fax: (206) 884-7594. E-mail: craig.rubens{at}seattlechildrens.org

{triangledown} Published ahead of print on 13 October 2008.

{ddagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: A. J. Bäumler

{dagger} Present address: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD.

Infection and Immunity, December 2008, p. 5862-5872, Vol. 76, No. 12
0019-9567/08/$08.00+0     doi:10.1128/IAI.00865-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Montgomery, C. P., Daum, R. S. (2009). Transcription of Inflammatory Genes in the Lung after Infection with Community-Associated Methicillin-Resistant Staphylococcus aureus: a Role for Panton-Valentine Leukocidin?. Infect. Immun. 77: 2159-2167 [Abstract] [Full Text]  


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