HIV-1 infection depletes human CD34+CD38- hematopoietic progenitor cells via pDC-dependent mechanisms

• Published in: PLoS pathogens Vol. 13; no. 7; p. e1006505
• Main Authors: Li, Guangming, Zhao, Juanjuan, Cheng, Liang, Jiang, Qi, Kan, Sheng, Qin, Enqiang, Tu, Bo, Zhang, Xin, Zhang, Liguo, Su, Lishan, Zhang, Zheng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.07.2017; Public Library of Science (PLoS)
• Subjects: Abnormalities; ADP-ribosyl Cyclase 1 - genetics; ADP-ribosyl Cyclase 1 - immunology; Animals; Antigens, CD34 - immunology; Biology and Life Sciences; Biophysics; Bone marrow; Cancer; CD34 antigen; CD38 antigen; Cells (biology); Chronic infection; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - virology; Depletion; Funding; Gene expression; Hematopoiesis; Hematopoietic stem cells; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - immunology; Hematopoietic Stem Cells - virology; HIV; HIV Infections - immunology; HIV Infections - virology; HIV-1 - physiology; Hospitals; Human immunodeficiency virus; Humans; Infections; Infectious diseases; Laboratories; Medical research; Medicine and Health Sciences; Mice; Mice, Inbred BALB C; Pancytopenia; Pathogenesis; Patients; Research and Analysis Methods; Rodents; Roles; Science; Software; Stem cells; Viruses; Beijing China; China
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1006505

Chronic human immunodeficiency virus-1 (HIV-1) infection in patients leads to multi-lineage hematopoietic abnormalities or pancytopenia. The deficiency in hematopoietic progenitor cells (HPCs) induced by HIV-1 infection has been proposed, but the relevant mechanisms are poorly understood. We report here that both human CD34+CD38- early and CD34+CD38+ intermediate HPCs were maintained in the bone marrow (BM) of humanized mice. Chronic HIV-1 infection preferentially depleted CD34+CD38- early HPCs in the BM and reduced their proliferation potential in vivo in both HIV-1-infected patients and humanized mice, while CD34+CD38+ intermediate HSCs were relatively unaffected. Strikingly, depletion of plasmacytoid dendritic cells (pDCs) prevented human CD34+CD38- early HPCs from HIV-1 infection-induced depletion and functional impairment and restored the gene expression profile of purified CD34+ HPCs in humanized mice. These findings suggest that pDCs contribute to the early hematopoietic suppression induced by chronic HIV-1 infection and provide a novel therapeutic target for the hematopoiesis suppression in HIV-1 patients.