Chlamydia trachomatis stimulation enhances HIV-1 susceptibility via the modulation of a member of the macrophage inflammatory proteins.

Sexually transmitted infections (STI) such as Chlamydia trachomatis (CT) can enhance human immunodeficiency virus type one (HIV-1) infection. However, the molecular mechanisms modulating the enhancement of HIV-1 infectivity and replication during HIV-1/STIs coinfection remain elusive. In this study, we performed an ex vivo infection of HIV-1 in peripheral blood mononuclear cells (PBMCs) of C. trachomatis-infected patients and observed a significant increase in HIV-1 p24 levels as compared to cells from healthy donors. Similarly, C. trachomatis-stimulated PBMCs from healthy donors showed enhanced susceptibility to HIV-1. C. trachomatis-stimulated CD4 T cells also harboured more HIV-1 copy numbers. RNA-seq data revealed the upregulation of CCL3L1/CCL3L3, a paralog of CCL3 in C. trachomatis-stimulated CD4 T cells infected with HIV-1. Furthermore, an increase in CCL3L1/CCL3L3 expression levels correlated with HIV-1 replication in C. trachomatis-stimulated cells. However, the addition of exogenous CCL3L1 reduces HIV-1 infection of healthy cells, indicating a dual role of CCL3L1 in HIV-1 infection. Further investigation revealed that knockout of CCL3L1/CCL3L1 in Jurkat T cells rescued the increased susceptibility of C. trachomatis-stimulated cells to HIV-1 infection. These results reveal a role for CCL3L1/CCL3L3 in enhancing HIV-1 replication and production and highlight a mechanism for the enhanced susceptibility to HIV-1 among C. trachomatis-infected patients.