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    Pulmonary Immunostimulation with MALP-2 in Influenza Virus-Infected Mice Increases Survival after Pneumococcal Superinfection (2015)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Reppe, Katrin
    Radünzel, Peter
    Dietert, Kristina (WE 12)
    Tschernig, Thomas
    Wolff, Thorsten
    Hammerschmidt, Sven
    Gruber, Achim D (WE 12)
    Suttorp, Norbert
    Witzenrath, Martin
    Quelle
    Infection and immunity; 83(12) — S. 4617–4629
    ISSN: 0019-9567
    Sprache
    Englisch
    Verweise
    DOI: 10.1128/IAI.00948-15
    Pubmed: 26371127
    Kontakt
    Institut für Tierpathologie

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    Gebäude 12
    14163 Berlin
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    Abstract / Zusammenfassung

    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 of the pathogenesis of secondary bacterial lung infection. Thus, specific local stimulation of the pulmonary innate immune system in subjects with influenza virus infection might improve the host defense against secondary bacterial pathogens. In the present study, we examined the effect of pulmonary immunostimulation with Toll-like receptor 2 (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 the 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 the bacterial number in the lung tissue without inducing exaggerated inflammation. The pulmonary viral load was not altered by MALP-2. Clinically, MALP-2 treatment of IAV-infected mice increased survival rates and reduced hypothermia and body weight loss after pneumococcal superinfection compared to those of untreated coinfected mice. In conclusion, local immunostimulation with MALP-2 in influenza virus-infected mice improved pulmonary bacterial elimination and increased survival after subsequent pneumococcal superinfection.