The whole process of macrophage–Treponema pallidum interactions: Opsonic phagocytosis, nonopsonic phagocytosis and active invasion

Despite the acknowledged central role of opsonophagocytosis in the process of syphilis, the interaction between Treponema pallidum and human macrophages during nonopsonophagocytosis and active invasion remains controversial. To investigate whether nonopsonic phagocytosis and active invasion, similar to opsonic phagocytosis, also participate in the process of macrophage-T. pallidum interactions, monocyte-derived macrophages were used to study the interactions of T. pallidum and macrophages in the presence of nonsyphytic or syphilitic serum and in the absence of serum in vitro using indirect immunofluorescence and flow cytometry to quantitate treponeme-macrophage interactions. The results showed that macrophages phagocytose T. pallidum under both nonopsonizing conditions (no serum or normal human serum (NHS)) and in the presence of opsonizing serum (secondary syphilitic serum (SSS)) in a time-dependent manner. The percentages of spirochete-positive macrophages in the SSS group were higher than those in the NHS and no-serum groups. Blocking FcγR or inactivating complement caused a significant decrease in the percentage of spirochete-positive macrophages in the SSS group but did not cause a decrease in the percentages of spirochete-positive macrophages in the NHS and no-serum groups. In addition, after inhibiting macrophage phagocytosis, approximately 30% of macrophages internalized spirochetes, verifying that T. pallidum actively penetrated macrophages rather than was ingested by them. This study provides evidence that opsonic phagocytosis, nonopsonic phagocytosis and active invasion are all active during T. pallidum-macrophage interactions and reveals a process of treponeme-macrophage interactions in T. pallidum pathogenesis.