TLR8 agonist selgantolimod regulates Kupffer cell differentiation status and impairs HBV entry into hepatocytes via an IL-6-dependent mechanism.

Achieving HBV cure will require novel combination therapies of direct-acting antivirals and immunomodulatory agents. In this context, the toll-like receptor 8 (TLR8) agonist selgantolimod (SLGN) has been investigated in preclinical models and clinical trials for chronic hepatitis B (CHB). However, little is known regarding its action on immune effectors within the liver. Our aim was to characterise the transcriptomic changes and intercellular communication events induced by SLGN in the hepatic microenvironment. We identified Hepatic Our transcriptomic characterisation of SLGN sheds light into the programmes regulating KC activation. Furthermore, in addition to its previously described effect on established HBV infection and adaptive immunity, we show that SLGN impairs HBV entry. Altogether, SLGN may contribute through KCs to remodelling the intrahepatic immune microenvironment and may thus represent an important component of future combinations to cure HBV infection.

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© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: FZ and BT received grants from Assembly, Beam Therapeutics, Blue Jay and JnJ; FZ had consulting activities with Assembly, Blue Jay and GSK. YCH receives grants from Gilead Sciences and Sysmex. FZ is an associate editor of the journal. SD, LL, NK, JJW, AHL, and SPF are or were employees of Gilead Sc.