Replication or death: distinct fates of pathogenic Leptospira strain Lai within macrophages of human or mouse origin

Pathogenic leptospires evoke severe diseases in humans but only cause mild chronic or asymptomatic infection in many host animals. The reasons for this diversity of infection remain unclear. Here, we demonstrated that Leptospira interrogans serovar Lai strain Lai had a similar ability to adhere to and enter primary and immortal (THP-1 and J774A.1) macrophages from human and mouse, but its intracellular fate in human macrophages differed markedly from that in mouse. The leptospires resided within membrane-bound vacuoles in the murine macrophages, but occurred free in the cytosol of human macrophages, with no surrounding vesicular membrane. Most leptospires in murine macrophages co-localized with the late-endosomal/lysosomal marker LAMP-1 and then were killed by lysosomal hydrolases, while most leptospires in human macrophages did not co-localize with this marker and survived. Enumeration of colony-forming units plus quantitative fluorimetry showed that in human, but not in murine, macrophages, the amounts of leptospires increased with incubation time. The infected human macrophages differed from mouse macrophages by displaying gradually enhanced apoptosis, in parallel with the increase in number of leptospires. These data strongly suggest that the outcome for intracellular leptospires depends on differences among host macrophages, which may account for some of the differences in the severity of leptospirosis in humans and animals.