title: A novel outbred mouse model of 2009 pandemic influenza and bacterial co-infection severity.
abstract: Influenza viruses pose a significant health risk and annually impose a great cost to patients and the health care system. The molecular determinants of influenza severity, often exacerbated by secondary bacterial infection, are largely unclear. We generated a novel outbred mouse model of influenza virus, Staphylococcus aureus, and co-infection utilizing influenza A/CA/07/2009 virus and S. aureus (USA300). Outbred mice displayed a wide range of pathologic phenotypes following influenza virus or co-infection ranging broadly in severity. Influenza viral burden positively correlated with weight loss although lung histopathology did not. Inflammatory cytokines including IL-6, TNF-α, G-CSF, and CXCL10 positively correlated with both weight loss and viral burden. In S. aureus infection, IL-1β, G-CSF, TNF-α, and IL-6 positively correlated with weight loss and bacterial burden. In co-infection, IL-1β production correlated with decreased weight loss suggesting a protective role. The data demonstrate an approach to identify biomarkers of severe disease and to understand pathogenic mechanisms in pneumonia.
authors: Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States of America.
authors: Kevin J
authors: KJ
authors: McHugh
authors: Sivanarayana
authors: S
authors: Mandalapu
authors: Jay K
authors: JK
authors: Kolls
authors: Ted M
authors: TM
authors: Ross
authors: John F
authors: JF
authors: Alcorn
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D058491:Bacterial Load; D002642:Chick Embryo; D060085:Coinfection; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression; D053118:Influenza A Virus, H1N1 Subtype; D009980:Influenza A virus; D008168:Lung / Q000382:microbiology / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D010641:Phenotype; D011014:Pneumonia / Q000235:genetics / Q000382:microbiology / Q000473:pathology / Q000821:virology; D013203:Staphylococcal Infections / Q000235:genetics / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D013211:Staphylococcus aureus; D019562:Viral Load; D015431:Weight Loss
chemical_list: D016207:Cytokines