E-prostanoid 2 receptor signaling suppresses lung innate immunity against Streptococcus pneumoniae

► EP2 receptor-deficient mice are protected from death from pneumococcal pneumonia. ► EP2 null mice have enhanced inflammatory responses to S. pneumoniae in the lungs. ► Alveolar macrophage phagocytosis of S. pneumoniae is suppressed by PGE2-EP2 signaling. ► PGE2 restricts pneumococcal killing by alveolar macrophages via the EP2 receptor. ► The EP2 receptor limits inflammatory mediator production by infected macrophages.