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Published on: April 14, 2011
Pulmonary immunostimulation with MALP-2 in influenza virus-infected mice increases survival after pneumococcal
Katrin Reppe1, Peter Radünzel1, Kristina Dietert2
1Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Abstract:
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.
Insights
Pulmonary immunostimulation with macrophage-activating lipopeptide 2 (MALP-2) enhances host defense against secondary bacterial pneumonia following influenza A virus (IAV) infection. This treatment improves bacterial clearance and survival rates in mice.
Area of Science:
- Immunology
- Infectious Diseases
- Pulmonology
Background:
- Influenza virus infection often leads to secondary bacterial pneumonia, particularly from Streptococcus pneumoniae.
- Local immunosuppression in the lungs post-influenza contributes to the pathogenesis of these superinfections.
- Targeting the pulmonary innate immune system may offer a strategy to combat secondary bacterial infections.
Purpose of the Study:
- To investigate the efficacy of pulmonary immunostimulation using Toll-like receptor 2 (TLR-2)-stimulating macrophage-activating lipopeptide 2 (MALP-2) in a mouse model of influenza A virus (IAV) and subsequent pneumococcal superinfection.
- To assess the impact of MALP-2 on immune cell recruitment, cytokine release, bacterial load, and clinical outcomes.
Main Methods:
- Female C57BL/6N mice were infected with IAV and subsequently treated with intratracheal MALP-2.
- Mice were challenged with Streptococcus pneumoniae 24 hours after MALP-2 administration.
- Immune responses, bacterial burden, viral load, and clinical parameters (body weight, temperature, survival) were evaluated.
Main Results:
- Intratracheal MALP-2 administration in IAV-infected mice increased proinflammatory cytokine and chemokine release and enhanced neutrophil recruitment to the lungs.
- MALP-2 treatment significantly reduced bacterial load in lung tissue without exacerbating inflammation or affecting viral load.
- MALP-2 treatment improved survival rates and ameliorated hypothermia and body weight loss in coinfected mice.
Conclusions:
- Local pulmonary immunostimulation with MALP-2 is a promising strategy to enhance host defense against pneumococcal superinfection following influenza virus infection.
- MALP-2 treatment effectively reduces bacterial burden and improves clinical outcomes, offering a potential therapeutic approach for influenza-associated bacterial pneumonia.
