A postinfluenza model of Staphylococcus aureus pneumonia.
BACKGROUND
Postinfluenza Staphylococcus aureus pneumonias are increasingly recognized as a major form of life-threatening infections.


METHODS
A mouse model of postinfluenza S. aureus pneumonia was developed. Mice were intranasally infected with bacteria alone or bacteria plus virus. Infection was assessed by mouse survival, lung histopathology, bacterial density in the lungs, and cellular response to infection.


RESULTS
Mice infected with both influenza virus and S. aureus showed higher mortality, greater lung parenchymal damage, and greater bacterial density at metastatic tissue sites than mice infected with only S. aureus. At 4 h, more polymorphonuclear leukocytes and fewer CD11c(+) cells were found in lung samples from mice infected with virus and bacteria than in those from mice infected with bacteria. alpha-Hemolysin and protein A were maximally expressed 4 h after infection, and Panton-Valentine leukocidin was maximally expressed 72 h after infection, with higher levels of alpha-hemolysin expression in mice infected with bacteria alone. Interferon gamma expression was higher in tissue collected from mice infected with virus plus bacteria than in those from bacteria-infected mice.


CONCLUSIONS
The results from this model demonstrate diverse effects caused by antecedent influenza virus infection, which have a profound influence on the morbidity and mortality associated with S. aureus pneumonia.
Lee
Mei-Ho
MH
Division of Infectious Diseases, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Arrecubieta
Carlos
C
Martin
Francis J
FJ
Prince
Alice
A
Borczuk
Alain C
AC
Lowy
Franklin D
FD
D000704:Analysis of Variance; D000818:Animals; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000235:genetics; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005098:Exotoxins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D006460:Hemolysin Proteins / Q000096:biosynthesis / Q000235:genetics; D006651:Histocytochemistry; D053118:Influenza A Virus, H1N1 Subtype / Q000254:growth & development; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007956:Leukocidins / Q000096:biosynthesis / Q000235:genetics; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000382:microbiology* / Q000503:physiopathology; D011023:Pneumonia, Staphylococcal / Q000382:microbiology / Q000503:physiopathology / Q000821:virology*; D013205:Staphylococcal Protein A / Q000096:biosynthesis / Q000235:genetics; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D018709:Statistics, Nonparametric
D001427:Bacterial Toxins; D005098:Exotoxins; D006460:Hemolysin Proteins; D007956:Leukocidins; C078284:Panton-Valentine leukocidin; D013205:Staphylococcal Protein A; C021091:staphylococcal alpha-toxin; D007371:Interferon-gamma