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Mechanical Ventilation Alters the Development of Staphylococcus aureus Pneumonia in Rabbit
Saber-Davide Barbar1, Laure-Anne Pauchard1, Rémi Bruyère1
1Laboratoire "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.
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.
Insights
Mechanical ventilation (MV) worsens ventilator-associated pneumonia (VAP) by increasing inflammation and bacterial load, potentially via toll-like receptor 2 (TLR2) upregulation. This study highlights MV
Area of Science:
- Immunology
- Pulmonology
- Microbiology
Background:
- Ventilator-associated pneumonia (VAP) is a frequent complication of mechanical ventilation (MV).
- MV may exacerbate VAP by promoting a pro-inflammatory immune response, possibly through toll-like receptor (TLR) activation.
Purpose of the Study:
- To investigate the hypothesis that MV upregulates TLRs, contributing to increased severity of Staphylococcus aureus VAP.
- To assess the impact of MV on host immune response and bacterial clearance in a rabbit VAP model.
Main Methods:
- A rabbit model of Staphylococcus aureus VAP was established in spontaneously breathing (SB) and mechanically ventilated (MV) groups.
- Pulmonary and systemic bacterial burden, inflammatory markers (IL-8, TNF-α), and TLR2 expression were evaluated at 8 and 24 hours post-infection.
- Ex vivo whole blood stimulation assays using TLR2 agonists or heat-killed S. aureus were performed.
Main Results:
- MV rabbits exhibited more severe lung injury, higher bacterial concentrations, and elevated serum IL-8 and TNF-α levels compared to SB rabbits at 8 hours.
- Whole blood from MV rabbits showed increased cytokine release upon stimulation with TLR2 agonists or heat-killed S. aureus.
- MV induced TLR2 overexpression in lung and spleen tissues.
Conclusions:
- Mechanical ventilation exacerbates VAP by increasing tissue injury, impairing bacterial clearance, and promoting systemic inflammation.
- TLR2 overexpression may be a key mechanism underlying the adverse effects of MV on host immune response in VAP.
