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

Autor: Li G; The Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States of America., Zhao J; Research Center for Clinical & Translational Medicine, Beijing 302 Hospital, Beijing, China., Cheng L; The Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States of America., Jiang Q; The Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States of America., Kan S; Research Center for Clinical & Translational Medicine, Beijing 302 Hospital, Beijing, China., Qin E; Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China., Tu B; Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China., Zhang X; Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China., Zhang L; Key laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Science, Beijing, China., Su L; The Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States of America.; Key laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Science, Beijing, China., Zhang Z; The Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States of America.; Research Center for Clinical & Translational Medicine, Beijing 302 Hospital, Beijing, China.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2017 Jul 31; Vol. 13 (7), pp. e1006505. Date of Electronic Publication: 2017 Jul 31 (Print Publication: 2017).
DOI: 10.1371/journal.ppat.1006505
Abstrakt: 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.
Databáze: MEDLINE
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