Several limitations of our study should be mentioned. First, the MV with “high” VT and without PEEP we used could be considered not clinically relevant. However, it has recently been reported that such settings were still used, especially in the operating room . In addition, it is known that lung injury is heterogeneous in ARDS patients. As a result, poorly aerated areas of the lung usually coexist with overstretched ones, even if “low-VT” is applied, as shown in human studies . It is therefore quite possible that such parts of the lung may react as described in the present study if bacterial challenge occurred in patients subjected to “protective” MV. Third, TLR2 assessment was limited to gene expression, and the corresponding protein was not measured. Fourth, our study may be underpowered given the small size of the experimental groups. In addition, we should acknowledge that the LNZ concentrations achieved in the treated animals did not reach the usually reported values in humans, thereby undermining the clinical relevance of our findings (Fig 7). However, we used a MRSA strain, for which the MIC for LNZ was low (i.e., 1 mg/L). In addition, it has recently been shown that the LNZ concentration actually obtained in critically ill patients, especially those with lung injury, were probably not as high as those in healthy volunteers . Finally, our model does not exactly mimic the pathophysiology of VAP since a large number of bacteria were directly inoculated into the airways rather than repeatedly inhaled in small numbers. In addition, there was no mortality attributable to pneumonia in our model, at least over the 48-hour observation period. As a result it remains difficult to evaluate the clinical relevance of our findings.