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Updated: Jun 28, 2026
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Immunostimulation with macrophage-activating lipopeptide-2 increased survival in murine pneumonia
Katrin Reppe1, Thomas Tschernig, Anke Lührmann
1Department of Internal Medicine, Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Abstract:
Community-acquired pneumonia (CAP) is associated with high morbidity and mortality, and Streptococcus pneumoniae is the most prevalent causal pathogen identified in CAP. Impaired pulmonary host defense increases susceptibility to pneumococcal pneumonia. S. pneumoniae may up-regulate Toll-like receptor (TLR)-2 expression and activate TLR-2, contributing to pneumococcus-induced immune responses. In the current study, the course of severe murine pneumococcal pneumonia after pulmonary TLR-2-mediated immunostimulation with synthetic macrophage-activating lipopeptide-2 (MALP-2) was examined. Intratracheal MALP-2 application evoked enhanced proinflammatory cytokine and chemokine release, resulting in recruitment of polymorphonuclear neutrophils (PMN), macrophages, and lymphocytes into the alveolar space in WT, but not in TLR-2-deficient mice. In murine lungs as well as in human alveolar epithelial cells (A549), MALP-2 increased TLR-2 expression at both mRNA and protein level. Blood leukocyte numbers and populations remained unchanged. MALP-2 application 24 hours before intranasal pneumococcal infection resulted in increased levels of CCL5 associated with augmented leukocyte recruitment, and decreased levels of anti-inflammatory IL-10 in bronchoalveolar lavage fluid. Clinically, MALP-2-treated as compared with untreated mice showed increased survival, reduced hypothermia, and increased body weight. MALP-2 also reduced bacteremia and improved bacterial clearance in lung parenchyma, as examined by immunohistochemistry. In conclusion, pulmonary immunostimulation with MALP-2 before infection with S. pneumoniae improved local host defense and increased survival in murine pneumococcal pneumonia.
Insights
Stimulating Toll-like receptor (TLR)-2 with MALP-2 enhanced immune responses against Streptococcus pneumoniae pneumonia in mice. This immunostimulation improved survival and bacterial clearance, offering a potential therapeutic strategy for community-acquired pneumonia.
Area of Science:
- Immunology
- Microbiology
- Pulmonology
Background:
- Community-acquired pneumonia (CAP) presents significant morbidity and mortality, with Streptococcus pneumoniae as a primary pathogen.
- Impaired pulmonary defenses heighten susceptibility to pneumococcal pneumonia.
- Streptococcus pneumoniae may influence Toll-like receptor (TLR)-2 expression, impacting immune responses.
Purpose of the Study:
- To investigate the effects of pulmonary TLR-2-mediated immunostimulation using synthetic macrophage-activating lipopeptide-2 (MALP-2) on severe murine pneumococcal pneumonia.
- To assess the impact of MALP-2 on immune cell recruitment, cytokine profiles, and clinical outcomes in a murine model of pneumococcal pneumonia.
Main Methods:
- Administration of MALP-2 intratracheally in wild-type (WT) and TLR-2-deficient mice.
- Induction of pneumococcal pneumonia via intranasal inoculation.
- Analysis of bronchoalveolar lavage fluid for cytokine/chemokine levels and leukocyte populations.
- Evaluation of clinical parameters including survival, body weight, and hypothermia.
- Assessment of bacterial load in lung tissue using immunohistochemistry.
Main Results:
- MALP-2 treatment led to increased proinflammatory cytokine and chemokine release, recruiting polymorphonuclear neutrophils, macrophages, and lymphocytes in WT mice.
- MALP-2 upregulated TLR-2 expression in murine lungs and human alveolar epithelial cells (A549).
- Pre-infection MALP-2 administration resulted in elevated CCL5, reduced anti-inflammatory IL-10, improved survival, reduced hypothermia, increased body weight, decreased bacteremia, and enhanced bacterial clearance.
Conclusions:
- Pulmonary immunostimulation with MALP-2 effectively enhances local host defense against Streptococcus pneumoniae.
- Pre-emptive MALP-2 treatment significantly improves survival rates and reduces bacterial burden in a murine model of pneumococcal pneumonia.
- TLR-2 activation via MALP-2 represents a promising therapeutic avenue for managing pneumococcal pneumonia.
