Abstract
Required mechanical ventilation (MV) may contribute to bacterial dissemination in patients with Streptococcus pneumoniae pneumonia. Significant variations in plasma mitochondrial DNA (mtDNA) have been reported in sepsis according to the outcome. The impact of lung stretch during MV was addressed in a model of pneumonia. Healthy or S. pneumoniae infected rabbits were submitted to MV or kept spontaneously breathing (SB). Bacterial burden, cytokines release, mitochondrial DNA levels, integrity and transcription were assessed along with 48-hour mortality. Compared with infected SB rabbits, MV rabbits developed more severe pneumonia with greater concentrations of bacteria in the lungs, higher rates of systemic dissemination, higher levels of circulating inflammatory mediators and decreased survival. Pulmonary mtDNA levels were significantly lower in infected animals as compared to non-infected ones, whenever they were SB or MV. After a significant early drop, circulating mtDNA levels returned to baseline values in the infected SB rabbits, but remained low until death in the MV ones. Whole blood ex-vivo stimulation with Streptococcus pneumoniae resulted in a reduction of polymorphonuclear leukocytes mitochondrial density and plasma mtDNA concentrations. Thus, persistent mitochondrial depletion and dysfunction in the infected animals submitted to MV could account for their less efficient immune response against S. pneumoniae.
Highlights
Community acquired pneumonia remains the main cause of death from infection, and Streptococcus pneumoniae is the main bacterial agent[1]
Since mitochondrial density is thought to depend on mitochondrial biogenesis, we investigated the impact of mechanical ventilation (MV) and S. pneumoniae pneumonia on these pathways within the lung
We showed that PMN chemotaxis was decreased within the lung of infected animals subjected to MV independently from IL-8 production, together with the release of larger amounts of IL-10, a powerful anti-inflammatory cytokine
Summary
Community acquired pneumonia remains the main cause of death from infection, and Streptococcus pneumoniae is the main bacterial agent[1]. It is likely that the combination of the damaging effects of MV on the lungs (i.e., Ventilator-Induced Lung Injury [VILI], release of pro-inflammatory cytokines, recruitment and activation of polymorphonuclear leukocytes [PMNs]) and the onset of infection influences the severity of the disease[4,5,6,7]. This pro-inflammatory state could alter host defenses against bacterial invasion[8,9,10]. Our investigation was focused on whether MV and S. pneumoniae pneumonia could induce quantitative and qualitative mtDNA abnormalities in a rabbit model of infection[20]
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