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)-alphaserum 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-alpha: 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. Copyright © 2016 Barbar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Barbar, S. D., Pauchard, L. A., Bruyère, R., Bruillard, C., Hayez, D., Croisier, D., … Charles, P. E. (2016). Mechanical ventilation alters the development of Staphylococcus aureus pneumonia in rabbit. PLoS ONE, 11(7). https://doi.org/10.1371/journal.pone.0158799