title: Mechanical Ventilation Alters the Development of Staphylococcus aureus Pneumonia in Rabbit.
abstract: Ventilator-associated pneumonia (VAP) is common during mechanical ventilation (MV). Beside obvious deleterious effects on muco-ciliary clearance, MV could adversely shift the host immune response towards a pro-inflammatory pattern through toll-like receptor (TLRs) up-regulation. We tested this hypothesis in a rabbit model of Staphylococcus aureus VAP. Pneumonia was caused by airway challenge with S. aureus, in either spontaneously breathing (SB) or MV rabbits (n = 13 and 17, respectively). Pneumonia assessment regarding pulmonary and systemic bacterial burden, as well as inflammatory response was done 8 and 24 hours after S. aureus challenge. In addition, ex vivo stimulations of whole blood taken from SB or MV rabbits (n = 7 and 5, respectively) with TLR2 agonist or heat-killed S. aureus were performed. Data were expressed as mean±standard deviation. After 8 hours of infection, lung injury was more severe in MV animals (1.40±0.33 versus [vs] 2.40±0.55, p = 0.007), along with greater bacterial concentrations (6.13±0.63 vs. 4.96±1.31 colony forming units/gram, p = 0.002). Interleukin (IL)-8 and tumor necrosis factor (TNF)-αserum concentrations reached higher levels in MV animals (p = 0.010). Whole blood obtained from MV animals released larger amounts of cytokines if stimulated with TLR2 agonist or heat-killed S. aureus (e.g., TNF-α: 1656±166 vs. 1005±89; p = 0.014). Moreover, MV induced TLR2 overexpression in both lung and spleen tissue. MV hastened tissue injury, impaired lung bacterial clearance, and promoted a systemic inflammatory response, maybe through TLR2 overexpression.
authors.affiliation: Laboratoire "Ventilation Immunité Poumon", Pôle Microbiologie Environnementale et Risque Sanitaire (M.E.R.S.), U.M.R. 1347, I.N.R.A., Université de Bourgogne, Dijon, France.
authors.forename: Saber-Davide
authors.initials: SD
authors.lastname: Barbar
authors.affiliation: Laboratoire "Ventilation Immunité Poumon", Pôle Microbiologie Environnementale et Risque Sanitaire (M.E.R.S.), U.M.R. 1347, I.N.R.A., Université de Bourgogne, Dijon, France.
authors.forename: Laure-Anne
authors.initials: LA
authors.lastname: Pauchard
authors.affiliation: Laboratoire "Ventilation Immunité Poumon", Pôle Microbiologie Environnementale et Risque Sanitaire (M.E.R.S.), U.M.R. 1347, I.N.R.A., Université de Bourgogne, Dijon, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Bruyère
authors.affiliation: Laboratoire "Ventilation Immunité Poumon", Pôle Microbiologie Environnementale et Risque Sanitaire (M.E.R.S.), U.M.R. 1347, I.N.R.A., Université de Bourgogne, Dijon, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bruillard
authors.affiliation: Vivexia S.A.R.L., Gemeaux, France.
authors.forename: Davy
authors.initials: D
authors.lastname: Hayez
authors.affiliation: Vivexia S.A.R.L., Gemeaux, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Croisier
authors.affiliation: Intensive Care Laboratory, University Hospitals of Geneva, and Department of Microbiology and Molecular Medicine, Faculty of Medicine, 1211 Geneva 14, Switzerland.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Pugin
authors.affiliation: Laboratoire "Ventilation Immunité Poumon", Pôle Microbiologie Environnementale et Risque Sanitaire (M.E.R.S.), U.M.R. 1347, I.N.R.A., Université de Bourgogne, Dijon, France.
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Charles
mesh_terms: D000818:Animals; D016209:Interleukin-8 / Q000276:immunology; D011023:Pneumonia, Staphylococcal / Q000276:immunology* / Q000473:pathology; D053717:Pneumonia, Ventilator-Associated / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D011817:Rabbits; D012121:Respiration, Artificial; D013211:Staphylococcus aureus / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D016209:Interleukin-8; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha