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Pulmonary immunostimulation with MALP-2 in influenza virus-infected mice increased survival after pneumococcal superinfection

tetano

Editor, Senior Moderator
nfect Immun. 2015 Sep 14. pii: IAI.00948-15. [Epub ahead of print] [h=1]Pulmonary immunostimulation with MALP-2 in influenza virus-infected mice increased survival after pneumococcal superinfection.[/h] Reppe K[SUP]1[/SUP], Rad?nzel P[SUP]1[/SUP], Dietert K[SUP]2[/SUP], Tschernig T[SUP]3[/SUP], Wolff T[SUP]4[/SUP], Hammerschmidt S[SUP]5[/SUP], Gruber AD[SUP]2[/SUP], Suttorp N[SUP]1[/SUP], Witzenrath M[SUP]6[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] Pulmonary infection with influenza virus is frequently complicated by bacterial superinfection with Streptococcus pneumoniae being the most prevalent causal pathogen and hence, often associated with high morbidity and mortality rates. Local immunosuppression due to pulmonary influenza virus infection has been identified as a major cause in the pathogenesis of secondary bacterial lung infection. Thus, specific local stimulation of the pulmonary innate immune system in subjects with influenza infection might improve host defense against secondary bacterial pathogens. Here, we examined the effect of pulmonary immunostimulation with TLR-2 stimulating macrophage-activating lipopeptide-2 (MALP-2) in influenza A virus (IAV)-infected mice on the course of subsequent pneumococcal superinfection. Female C57BL/6N mice infected with IAV were treated with MALP-2 on day 5 and challenged with S. pneumoniae on day 6. Intratracheal MALP-2 application increased proinflammatory cytokine and chemokine release and enhanced recruitment of leukocytes, mainly neutrophils into the alveolar space of IAV-infected mice without detectable systemic side effects. Local pulmonary instillation of MALP-2 in IAV-infected mice 24 h before transnasal pneumococcal infection considerably reduced bacterial numbers in the lung tissue without inducing exaggerated inflammation. Pulmonary viral load was not altered by MALP-2. Clinically, MALP-2 treatment in IAV-infected mice increased survival rates and reduced hypothermia and body weight loss after pneumococcal superinfection compared with untreated co-infected mice. In conclusion, local immunostimulation with MALP-2 in influenza virus-infected mice improved pulmonary bacterial elimination and increased survival after subsequent pneumococcal superinfection.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.


PMID: 26371127 [PubMed - as supplied by publisher]
 
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