Objectives

Chlamydia (C.) trachomatis infects the female genital tract and may cause permanent tissue damage.The exact mechanism of bacterial clearance and development of tissue damage is still unknown. Our previous work has focused on the role of neutrophils on bacterial clearance and tissue destruction. Little is known about other myeloid cells in the female genital tract at steady state and during chlamydial infection. In this project, we characterize the recruitment of myeloid subpopulations and their impact on chlamydial infection and tissue damage.

Methods

In a C. muridarum infection mouse model, we investigated the infiltration of myeloid cells, bacterial load and tissue damage in the genital tract. The contribution of neutrophils was characterized in mice deficient in mature neutrophils (Mcl-1 mice). The effect of monocytes/inflammatory macrophages was investigated in CCR2-KO mice deficient in the recruitment of inflammatory monocytes.

Results

Myeloid cells infiltrated the genital tract early in infection, with a maximum for neutrophils and macrophages at 7 dpi, and for dendritic cells at 14 dpi. Chlamydial DNA was detected early in the upper genital tract. Chlamydia was efficently cleared at 31- 35 dpi from all parts of the genital tract. Mcl-1 mice lacking neutrophils showed substantial alterations of the inflammatory infiltrate and had higher chlamydial burden and reduced tissue damage. In wt mice, upon entry into the genital tract, inflammatory monocytes differentiated into macrophages and gave rise to different subpopulations. In CCR2-KO mice, the accumulation of macrophages was reduced, which suggests that the increase in macrophages in infected tissue is caused by recruitment and differentiation of inflammatory monocytes. CCR2-deficiency did not affect infiltration of neutrophils, DCs or T cells but reduced cytokine production by T cells.

Conclusions and Outlook

Neutrophils play a substantial role in chlamydial clearance and tissue destruction. Our data indicate the differential presence of individual subgroups of monocytes/macrophages during the course of infection, which may play different roles in immune reaction and tissue destruction.