Chlamydia trachomatis Stimulation Enhances HIV-1 Susceptibility through the Modulation of a Member of the Macrophage Inflammatory Proteins

作者：Dzakah, Emmanuel Enoch; Zhao, Jiacong; Wang, Liuyan; Rashid, Farooq; Xu, Ru; Yang, Ligang; Wan, Zhengwei; Huang, Liping; Wang, Haiying; Chen, Shuyi; Ke, Wujian; Kyei, Foster; Deng, Kai; Tang, Shixing^*

来源：Journal of Investigative Dermatology, 2022, 142(5): 1338-+.

DOI：10.1016/j.jid.2021.09.020

• SEXUALLY-TRANSMITTED INFECTIONS
• IMMUNODEFICIENCY-VIRUS TYPE-1
• HIGH-RISK WOMEN
• TRANSMISSION
• CCL3L1
• PATHOGENESIS
• DYNAMICS
• SYPHILIS
• IMMUNITY
• DISEASES

Sexually transmitted infections such as Chlamydia trachomatis can enhance HIV-1 infection. However, the molecular mechanisms modulating the enhancement of HIV-1 infectivity and replication during HIV-1/sexually transmitted infections coinfection remain elusive. In this study, we performed an ex vivo infection of HIV-1 in PBMCs of C. trachomatis-infected patients and observed a significant increase in HIV-1 p24 levels compared with those in 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 harbored more HIV-1 copy numbers. RNA sequencing 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 a knockout of CCL3L1/CCL3L3 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.

• 单位
  中国科学院研究生院; 中山大学; 南方医科大学