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Objective  To identify the major infiltrating phagocytes during leptospirosis and examine the killing mechanism used by the host to eliminate  Leptospira interrogans .    Methods  Major infiltrating phagocytes in  Leptospira -infected C3H/HeJ mice were detected by immunohistochemistry. Chemokines and vascular endothelial cell adhesion molecules (VECAMs) of  Leptospira -infected mice and leptospirosis patients were detected by microarray and immunohistochemistry.  Leptospira -phagocytosing and -killing abilities of human or mouse macrophages and neutrophils, and the roles of intracellular ROS, NO and [Ca 2+ ]i in  Leptospira -killing process were evaluated by confocal microscopy and spectrofluorimetry.    Results  Peripheral blood mononuclear-macrophages rather than neutrophils were the main infiltrating phagocytes in the lungs, liver and kidneys of infected mice. Levels of macrophage- but not neutrophil-specific chemokines and VECAMs were significantly increased in the samples from infected mice and patients. All macrophages tested had a higher ability than neutrophils to phagocytose and kill leptospires. Higher ROS and NO levels and [Ca 2+ ]i in the macrophages were involved in killing leptospires. Human macrophages displayed more phagolysosome formation and a stronger leptospire-killing ability to than mouse macrophages.    Conclusions  Mononuclear-macrophages but not neutrophils represent the main infiltrating and anti-leptospiral phagocytes during leptospirosis. A lower level of phagosome-lysosome fusion may be responsible for the lower  Leptospira -killing ability of human macrophages.

Mononuclear-macrophages but not neutrophils act as major infiltrating anti-leptospiral phagocytes during leptospirosis