Inhibition of Chlamydia trachomatis replication in HEp-2 cells by human monocyte-derived macrophages

Monocytes (M) and macrophages are important components of the immune response to foreign agents. Using an in vitro system, we studied the influence of human M and M-derived macrophages (MdM) on the replication of Chlamydia trachomatis (L2/434) in HEp-2 cells. M or MdM were added to infected cells at a ratio of 4:1, and the resultant chlamydial yield was evaluated in one-step growth experiments. Chlamydial DNA production was evaluated by dot hybridization. Both M and MdM reduced chlamydial yield and DNA production, but the reductions caused by MdM were more pronounced. Electron microscopy showed that while control HEp-2 cells at 48 h postinfection contained large inclusions in which most particles were elementary bodies, the infected HEp-2 cells exposed to MdM contained small vacuoles with abnormal reticulate bodies and very few typical elementary bodies. Separation of the MdM from the HEp-2 cells by a membrane reduced the inhibitory effect of the MdM relative to that of MdM in direct contact with the infected cells. Addition of tumor necrosis factor antibodies to C. trachomatis-infected HEp-2 cells exposed to MdM (either in direct contact or separated by a membrane from the infected cells) reduced the inhibition of chlamydial DNA production. These data suggest the possibility that MdM may modulate C. trachomatis replication in vivo.