Details

Autor(en) / Beteiligte

• Steinwede, Kathrin
• Tempelhof, Ole
• Bolte, Kristine
• Maus, Regina
• Bohling, Jennifer
• Ueberberg, Bianca
• Länger, Florian
• Christman, John W
• Paton, James C
• Ask, Kjetil
• Maharaj, Shyam
• Kolb, Martin
• Gauldie, Jack
• Welte, Tobias
• Maus, Ulrich A

Titel

Local delivery of GM-CSF protects mice from lethal pneumococcal pneumonia

Ist Teil von

• The Journal of immunology (1950), 2011-11, Vol.187 (10), p.5346-5356

Ort / Verlag

United States

Erscheinungsjahr

2011

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• The growth factor GM-CSF has an important role in pulmonary surfactant metabolism and the regulation of antibacterial activities of lung sentinel cells. However, the potential of intra-alveolar GM-CSF to augment lung protective immunity against inhaled bacterial pathogens has not been defined in preclinical infection models. We hypothesized that transient overexpression of GM-CSF in the lungs of mice by adenoviral gene transfer (Ad-GM-CSF) would protect mice from subsequent lethal pneumococcal pneumonia. Our data show that intra-alveolar delivery of Ad-GM-CSF led to sustained increased pSTAT5 expression and PU.1 protein expression in alveolar macrophages during a 28-d observation period. Pulmonary Ad-GM-CSF delivery 2-4 wk prior to infection of mice with Streptococcus pneumoniae significantly reduced mortality rates relative to control vector-treated mice. This increased survival was accompanied by increased inducible NO synthase expression, antibacterial activity, and a significant reduction in caspase-3-dependent apoptosis and secondary necrosis of lung sentinel cells. Importantly, therapeutic treatment of mice with rGM-CSF improved lung protective immunity and accelerated bacterial clearance after pneumococcal challenge. We conclude that prophylactic delivery of GM-CSF triggers long-lasting immunostimulatory effects in the lung in vivo and rescues mice from lethal pneumococcal pneumonia by improving antibacterial immunity. These data support use of novel antibiotic-independent immunostimulatory therapies to protect patients against bacterial pneumonias.