Open AccessHIV-1 infection depletes human CD34+CD38- hematopoietic progenitor cells via pDC-dependent mechanisms
Author(s) -
Guangming Li,
Juanjuan Zhao,
Cheng Liu,
Qi Jiang,
Sheng Kan,
Enqiang Qin,
Bo Tang,
Xin Zhang,
Liguo Zhang,
Lishan Su,
Zheng Zhang
Publication year - 2017
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1006505
Subject(s) - cd38 , haematopoiesis , cd34 , progenitor cell , biology , immunology , bone marrow , pancytopenia , stem cell , virology , cancer research , microbiology and biotechnology
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.