Alveolar macrophages contribute to host defenses against influenza. Enhancing their function contributed to protection against influenza and other acute lethal pulmonary infections. Wild-type mice and Tg mice expressing GM-CSF in the lung were infected with influenza virus, and lung pathology, weight loss and mortality were measured. GM-CSF was also administered to lungs of wild-type mice that were infected with influenza virus. All Tg mice expressing GM-CSF in the lungs survived with greatly reduced weight loss and lung injury and histologic evidence of a rapid host inflammatory response that controlled infection vs. wild-type mice not expressing GM-CSF in the lungs. This resistance to influenza was abrogated by elimination of alveolar phagocytes, but not by depletion of T cells, B cells or neutrophils. Tg mice had far more alveolar macrophages than wild-type mice and were more resistant to influenza-induced apoptosis. Delivery of intranasal GM-CSF to wild-type mice also conferred influenza resistance. Therefore, GM-CSF confers resistance to influenza by enhancing innate immune mechanisms that depend on alveolar macrophages. Pulmonary delivery of GM-CSF is therefore useful for reducing the significant morbidity and mortality due to influenza virus and is similarly useful in pulmonary infection caused by other infectious viral and bacterial agents.Les macrophages alvéolaires contribuent aux défenses de lhôte contre la grippe. Laugmentation de leur fonction a contribué à la protection contre la grippe et contre dautres infections aiguës pulmonaires létales. Des souris de type sauvage et des souris Tg exprimant GM-CSF dans le poumon ont été infectées par le virus de la grippe, et la pathologie des poumons, la perte de poids et la mortalité ont été mesurées. Le GM-CSF a également été administré aux poumons de souris de type sauvage qui ont été infectées par le virus de la grippe. Toutes les souris Tg exprimant GM-CSF dans les poumons ont survécu avec une perte de poids
