title: Plasmacytoid dendritic cells promote HIV-1-induced group 3 innate lymphoid cell depletion.
abstract: Group 3 innate lymphoid cells (ILC3s) have demonstrated roles in promoting antibacterial immunity, maintaining epithelial barrier function, and supporting tissue repair. ILC3 alterations are associated with chronic inflammation and inflammatory disease; however, the characteristics and relevant regulatory mechanisms of this cell population in HIV-1 infection are poorly understood due in part to a lack of a robust model. Here, we determined that functional human ILC3s develop in lymphoid organs of humanized mice and that persistent HIV-1 infection in this model depletes ILC3s, as observed in chronic HIV-1-infected patients. In HIV-1-infected mice, effective antiretroviral therapy reversed the loss of ILC3s. HIV-1-dependent reduction of ILC3s required plasmacytoid dendritic cells (pDCs), IFN-I, and the CD95/FasL pathway, as targeted depletion or blockade of these prevented HIV-1-induced ILC3 depletion in vivo and in vitro, respectively. Finally, we determined that HIV-1 infection induces CD95 expression on ILC3s via a pDC- and IFN-I-dependent mechanism that sensitizes ILC3s to undergo CD95/FasL-mediated apoptosis. We conclude that chronic HIV-1 infection depletes ILC3s through pDC activation, induction of IFN-I, and CD95-mediated apoptosis.
authors: Zheng
authors: Z
authors: Zhang
authors: Liang
authors: L
authors: Cheng
authors: Juanjuan
authors: J
authors: Zhao
authors: Guangming
authors: G
authors: Li
authors: Liguo
authors: L
authors: Zhang
authors: Weiwei
authors: W
authors: Chen
authors: Weiming
authors: W
authors: Nie
authors: Natalia J
authors: NJ
authors: Reszka-Blanco
authors: Fu-Sheng
authors: FS
authors: Wang
authors: Lishan
authors: L
authors: Su
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000276:immunology; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D010950:Plasma Cells / Q000276:immunology* / Q000473:pathology; D019014:fas Receptor / Q000276:immunology
chemical_list: D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007370:Interferon Type I; D019014:fas Receptor