[HTML][HTML] Plasmacytoid dendritic cells promote HIV-1–induced group 3 innate lymphoid cell depletion

Z Zhang, L Cheng, J Zhao, G Li… - The Journal of …, 2015 - Am Soc Clin Investig
Z Zhang, L Cheng, J Zhao, G Li, L Zhang, W Chen, W Nie, NJ Reszka-Blanco, FS Wang…
The Journal of clinical investigation, 2015Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation