Interplay between HIV-1 innate sensing and restriction in mucosal dendritic cells: balancing defense and viral transmission

•DC-mediated type I IFN production has a crucial role in halting viral replication and inducing adaptive antiviral immune responses.•Mucosal Langerhans cells and submucosal dendritic cells display cell-intrinsic antiviral signature programs.•The concerted action of innate sensors, host restriction factors and viral evasion mechanisms impacts viral transmission and pathogenesis.

Innate sensing of HIV-1 by dendritic cells (DCs) initiates cell-intrinsic signalling programs that direct virus restriction and antiviral defenses. These responses include the production of type I interferon (IFN) and a large number of IFN-stimulated genes (ISGs) with a broad spectrum of antiviral effector functions. Initial interactions of HIV-1 at the mucosal surfaces with DC-expressed innate immune factors including cGAS, TRIM5α and SAMHD1 are predictive of viraemia, inflammation and disease pathogenesis. Here, we review the molecular basis of HIV-1 sensing in the two major mucosal DC subsets, that is, epithelial Langerhans cells and subepithelial CD11c+ conventional DCs. We discuss the concerted actions of the host restriction factors and innate sensors as well as viral evasion mechanisms in determining HIV-1 susceptibility to infection and directing antiviral adaptive immune responses.

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