Importance of CXC chemokine receptor 2 in alveolar neutrophil and exudate macrophage recruitment in response to pneumococcal lung infection

Background: Sustained neutrophilic infiltration is known to contribute to organ damage, such as acute lung injury. CXC chemokine receptor 2 (CXCR2) is the major receptor regulating inflammatory neutrophil recruitment in acute and chronic inflamed tissues. Whether the abundant neutrophil recruitment observed in severe pneumonia is essential for protective immunity against Streptococcus pneumoniae is poorly defined. Results: Here we show that CXCR2 KO compared to wild-type mice have a severely reduced recruitment of neutrophils and exudate macrophages that is associated with a massive bacterial outgrowth in distal airspaces after infection with S. pneumoniae, resulting in 100% mortality within three days. Furthermore, irradiated wild-type mice reconstituted with increasing amounts of CXCR2 KO bone marrow (10–25–50–75% KO) have correspondingly decreased numbers of both neutrophil and exudate macrophage recruitment that is associated with a step-wise increase in bacterial burden and a reciprocal step-wise decrease in survival in S. pneumoniae-induced pulmonary infection. Summary: These data show that CXC chemokine receptor 2 serves a previously unrecognized non-redundant role in the regulation of both neutrophil and exudate macrophage recruitment to the lung in response to S. pneumoniae infection.