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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\u2013mediated 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\u2013deficient 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\u2013treated 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.<\/jats:p>","DOI":"10.1165\/rcmb.2008-0071oc","type":"journal-article","created":{"date-parts":[[2008,10,17]],"date-time":"2008-10-17T21:32:28Z","timestamp":1224279148000},"page":"474-481","source":"Crossref","is-referenced-by-count":51,"title":["Immunostimulation with Macrophage-Activating Lipopeptide-2 Increased Survival in Murine Pneumonia"],"prefix":"10.1093","volume":"40","author":[{"given":"Katrin","family":"Reppe","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Infectious Diseases and Pulmonary Medicine, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Tschernig","sequence":"additional","affiliation":[{"name":"Institute of Functional and Applied Anatomy, 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