title: Efficient infection, activation, and impairment of pDCs in the BM and peripheral lymphoid organs during early HIV-1 infection in humanized rag2⁻/⁻γ C⁻/⁻ mice in vivo.
abstract: Although plasmacytoid dendritic cells (pDCs) are involved in HIV-1 pathogenesis, the precise mechanism of interaction between pDCs and HIV-1 in vivo is not clear. The conflicting reports in HIV-1-infected patients highlight the importance of studying the interaction between HIV-1 and pDCs in relevant in vivo models. The rag2/γC double knockout (DKO) mouse supports reconstitution of a functional human immune system in central and peripheral lymphoid organs. We report here that functional pDCs were developed in the BM and peripheral lymphoid organs in humanized DKO (DKO-hu) mice. We show that pDCs from both BM and spleen were activated and productively infected during early HIV infection. The activation level of pDCs correlated with that of CD4⁺ T-cell activation and apoptosis. Although CD4⁺ T cells were preferentially depleted, pDCs were maintained but functionally impaired in the BM and spleen of HIV-infected DKO-hu mice. We conclude that HIV-1 can efficiently infect, activate, and impair pDCs in the BM and spleen, in correlation with CD4⁺ T-cell depletion. The humanized mouse will serve as a relevant model to investigate the development and function of pDCs and their role during HIV-1 pathogenesis in vivo.
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. iguozhang@ibp.ac.cn
authors.forename: Liguo
authors.initials: L
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Jiang
authors.forename: Guangming
authors.initials: G
authors.lastname: Li
authors.forename: Jerry
authors.initials: J
authors.lastname: Jeffrey
authors.forename: Grigoriy I
authors.initials: GI
authors.lastname: Kovalev
authors.forename: Lishan
authors.initials: L
authors.lastname: Su
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology*; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004268:DNA-Binding Proteins; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D014183:Transplantation, Heterologous
chemical_list: D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse