Background: Schistosomiasis, a parasitic helminth infection, affects over 250 million people
worldwide. Blood-borne S. mansoni eggs either penetrate the gut wall to migrate into the lumen, or become trapped in
blood capillaries such as liver sinusoids.
Chronic Hepatitis B infection causes hepatic inflammation and necrosis, ultimately
leading to hepatocellular carcinoma (HCC) formation.
Coinfections with S. mansoni and hepatitis B virus (HBV) occur disproportionally often in endemic areas. This
project aimed to investigate their combined effects on autophagy.
Methods: Transgenic (tg) mice expressing all three forms of the HBV surface proteins (collectively
called HBsAg) were infected with S. mansoni at the age of 17 weeks. After 9 weeks of infection, the animals were sacrificed.
Liver-to-body weight ratios and serum ALT levels were determined. The liver transcriptome
was analyzed (NGS) and specific protein levels were quantified using western blotting.
Results were compared to those of infected wt-mice, as well as non-infected wt- and
tg-control animals.
Results: Male, but not female S. mansoni-infected, HBsAg-transgenic mice showed higher serum ALT levels than non-infected,
transgenic animals. Transcriptomics depicted no regulation of the autophagy-related
gene SQSTM1 between all groups. LC3 was upregulated in infected, tg-animals compared to wt-mice, with no differences
in regulation between all other groups. On protein level, tg-animals exhibited elevated
levels of p62, an autophagosome cargo protein, compared to all other groups. Additionally,
S. mansoni infection of both wt- as well as tg-mice caused elevated LC3B2 levels compared to
non-infected animals. Non-infected animals, on the other hand, showed higher levels
of LC3B1 in wt- and tg-animals.
Conclusion: Higher liver-to-bodyweight ratios of infected tg-animals show an additive effect
of both pathogens on hepatocellular damage. The male-specific increase in ALT levels
indicates an even stronger exacerbation in male mice.
Furthermore, the downregulation of p62 in tg-animals as well as the shift from high
LC3B1 to LC3B2 levels in both wt- and tg-animals caused by the infection with S. mansoni suggest a contrary effect of both pathogens on autophagy in a co-infection model.
