DNAX-Activating Protein of 12 kDa Impairs Host Defense in Pneumococcal Pneumonia

Objectives: Streptococcus pneumoniae is the most common causative organism in community-acquired pneumonia responsible for millions of deaths every year. DNAX-activating protein of 12 kDa is an adaptor molecule for different myeloid expressed receptors involved in innate immunity. Design: Animal study. Setting: University research laboratory. Subjects: DNAX-activating protein of 12 kDa-deficient (dap12(-/-)) and wild-type mice. Interventions: Mice were intranasally infected with S. pneumoniae. In addition, ex vivo responsiveness of alveolar macrophages was examined. Measurements and Main Results: dap12(-/-) alveolar macrophages released more tumor necrosis factor-a upon stimulation with S. pneumoniae and displayed increased phagocytosis of this pathogen compared with wild-type cells. After infection with S. pneumoniae via the airways, dap12(-/-) mice demonstrated reduced bacterial outgrowth in the lungs together with delayed dissemination to distant body sites relative to wild-type mice. This favorable response in dap12(-/-) mice was accompanied by reduced lung inflammation and an improved survival. Conclusions: These data suggest that DNAX-activating protein of 12 kDa impairs host defense during pneumococcal pneumonia at the primary site of infection at least in part by inhibiting phagocytosis by alveolar macrophages.