Production and release of hepatitis B virus particles in a 1.4-transgenic mouse model lead to increased phagocytic activity in Kupffer cells

Background and Aims Pathogenesis of Hepatitis B virus (HBV) infection is driven by the adaptive as well as the innate immune system. The present project aims to investigate how HBV surface antigen (HBsAg) affects Kupffer cell function, utilising different HBV-transgenic mouse strains.

Method F4/80-positive KC were prepared after two-step perfusion of murine livers (wild type, tg(Alb1HBV)44Bri (Alb/HBs), tg1.4HBV-s-mut and tg1.4HBV-s-rec [F1 generation of Alb/HBs × tg1.4HBV-s-mut]) followed by MACS bead separation. Phagocytic activity (PA) was analysed by flow cytometry. F4/80 was stained in Eci-cleared mouse liver and visualised by Light sheet fluorescence microscopy (LSFM).

Results Two populations of F4/80-positive KC (dim and bright) could be identified and were independently analysed. F4/80-bright KC derived from tg1.4HBV-s-rec mice and Alb/HBs-derived F4/80-dim KC showed decreased PA. Interestingly tg1.4HBV-s-rec-derived F4/80-dim KC showed significantly increased PA. Although the KC counts were significantly increased in tg1.4HBV-s-mut mice, F4/80-dim and -bright populations showed phagocytic activities and capacities related to wild type KC. Furthermore, in Eci-cleared liver tissue of tg1.4HBV-s-mut mice, compared to wild type samples, LSFM visualised a distinct distribution and signal intensity of F4/80+ cells within the liver lobular structure. The F4/80-related signal intensity was significantly decreased on KC in HBV-s-mut mice and further indicated a migration from peripheral/portal area towards the central area of liver lobules.

Conclusion The production and release of viral particles in tg1.4HBV-s-rec mice possibly lead to an increased phagocytic activity in F4/80-dim KC. Assuming, that KC function is not generally impaired in HBV-replicating murine models.

Publikationsverlauf

Artikel online veröffentlicht:
26. Januar 2022