Comment on “Nonhematopoietic Cells Are Key Players in Innate Control of Bacterial Airway Infection”

Using bone marrow chimeras, LeibundGut-Landmann et al. conclude in a recent study that nonhematopoietic cells are important to host defense in the lung against an intracellular pathogen, Legionella pneumophila (reviewed in Ref. 1). Neutrophils are a critical contributor to host defense in the lungs (2) because selective depletion of neutrophils results in substantial reduction in the clearance of Klebsiella pneumoniae and L. pneumophila organisms. Using bone marrow chimeras, we have shown that both hematopoietic and nonhematopoietic cells in the lungs are essential for neutrophil-dependent host defense against extracellular pathogens, including Escherichia coli (3) and K. pneumoniae (4). CXCL1/KC, CXCL2/MIP-2, CXCL5/LIX, and lungkine are the primary neutrophil chemokines in mice, and the receptor for these chemokines, CXCR2, is expressed on both hematopoietic and nonhematopoietic cells. KC and MIP-2 are produced by both hematopoietic and nonhematopoietic cells in the lung (2), whereas LIX and lungkine are secreted primarily by nonhematopoietic cells, such as epithelial cells (5, 6). Although the reported findings (1) are conclusive, neutrophil accumulation was measured within 28 h following infection and epithelial chemokines have not been measured. Nonetheless, these findings (1) lead us to wonder whether both hematopoietic and nonhematopoietic cells are important for neutrophil-dependent host defense to extracellular Gram-negative pathogens, or whether one of these cell types is necessary and/or sufficient to induce host defense against intracellular Gram-negative pathogens. These findings will have translational implications for harnessing innate immunity versus targeting the causative bacterium to combat multidrug-resistant bacteria and to develop potent vaccines against pulmonary infections.