RT Journal Article
SR Electronic
T1 Pulmonary immunostimulation with macrophage-activating lipopeptide-2 in influenza-A-virus infected mice increased survival of subsequent pneumococcal pneumonia
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 2816
VO 40
IS Suppl 56
A1 Katrin Reppe
A1 Peter Radünzel
A1 Thomas Tschernig
A1 Thorsten Wolff
A1 Achim Gruber
A1 Norbert Suttorp
A1 Martin Witzenrath
YR 2012
UL http://erj.ersjournals.com/content/40/Suppl_56/2816.abstract
AB Rationale: Secondary bacterial infections in the course of seasonal influenza virus epidemics are associated with high morbidity and mortality, and Streptococcus pneumoniae is the most prevalent causal pathogen. Local immunosuppression due to pulmonary influenza virus infection has been discussed as major cause in the pathogenesis of secondary bacterial lung infection. Thus, specific local stimulation of the pulmonary innate immune system might improve host defense against secondary bacterial pathogens.Methods: Influenza-A/H1N1/PR/8/34-virus infected female C57BL/6 mice received the TLR-2 ligand macrophage-activating lipopeptide-2 (MALP-2) intratracheally 24h prior to transnasal infection with S. pneumoniae.Results: Intratracheal application of MALP-2 increased pro-inflammatory cytokine and chemokine release and enhanced recruitment of leukocytes, mainly neutrophils in the alveolar space of influenza virus infected mice. After secondary pneumococcal infection, Influenza-A-virus infected mice pretreated with MALP-2 showed increased survival rates compared with untreated influenza infected mice. Notably, levels of pro-inflammatory cytokines and leukocytes were comparable in bronchoalveolar lavages of virus infected mice treated with MALP-2 and untreated infected controls. Further, MALP-2 significantly reduced bacterial numbers in the lung tissue without changing pulmonary viral load.Conclusion: Local immunostimulation with MALP-2 in influenza virus infected mice improved pulmonary bacterial elimination and increased survival in secondary pneumococcal pneumonia.