title: Combined action of influenza virus and Staphylococcus aureus panton-valentine leukocidin provokes severe lung epithelium damage.
abstract: Staphylococcus aureus necrotizing pneumonia is a life-threatening disease that is frequently preceded by influenza infection. The S. aureus toxin Panton-Valentine leukocidin (PVL) is most likely causative for necrotizing diseases, but the precise pathogenic mechanisms of PVL and a possible contribution of influenza virus remain to be elucidated. In this study, we present a model that explains how influenza virus and PVL act together to cause necrotizing pneumonia: an influenza infection activates the lung epithelium to produce chemoattractants for neutrophils. Upon superinfection with PVL-expressing S. aureus, the recruited neutrophils are rapidly killed by PVL, resulting in uncontrolled release of neutrophil proteases that damage the airway epithelium. The host counteracts this pathogen strategy by generating PVL-neutralizing antibodies and by neutralizing the released proteases via protease inhibitors present in the serum. These findings explain why necrotizing infections mainly develop in serum-free spaces (eg, pulmonary alveoli) and open options for new therapeutic approaches.
authors: Institute of Medical Microbiology, University Hospital of Münster, Germany.
authors: Silke
authors: S
authors: Niemann
authors: Christina
authors: C
authors: Ehrhardt
authors: Eva
authors: E
authors: Medina
authors: Kathrin
authors: K
authors: Warnking
authors: Lorena
authors: L
authors: Tuchscherr
authors: Vanessa
authors: V
authors: Heitmann
authors: Stephan
authors: S
authors: Ludwig
authors: Georg
authors: G
authors: Peters
authors: Bettina
authors: B
authors: Löffler
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism / Q000494:pharmacology*; D002457:Cell Extracts / Q000494:pharmacology; D002460:Cell Line; D017077:Culture Media, Conditioned; D004848:Epithelium / Q000276:immunology / Q000821:virology*; D005098:Exotoxins / Q000378:metabolism / Q000494:pharmacology*; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000276:immunology / Q000502:physiology*; D007251:Influenza, Human / Q000150:complications / Q000276:immunology / Q000473:pathology; D007956:Leukocidins / Q000378:metabolism / Q000494:pharmacology*; D008168:Lung / Q000276:immunology / Q000473:pathology* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000821:virology; D010447:Peptide Hydrolases / Q000378:metabolism; D011023:Pneumonia, Staphylococcal / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000276:immunology* / Q000378:metabolism; D019562:Viral Load
chemical_list: D001427:Bacterial Toxins; D002457:Cell Extracts; D017077:Culture Media, Conditioned; D005098:Exotoxins; D007956:Leukocidins; C078284:Panton-Valentine leukocidin; D011480:Protease Inhibitors; D010447:Peptide Hydrolases