Hepatitis B stimulates processes that deprive the body’s immune cells of key nutrients that they need to function, according to the latest research.
Led by UCL and funded by the Medical Research Council and Wellcome Trust, the research explains why the immune system cannot control hepatitis B virus infection once it becomes established in the liver, and offers a target for potential curative treatments in the future. The research also offers insights into controlling the immune system, which could be useful for organ transplantation and treating auto-immune diseases.
The study, published in Nature Medicine, suggests that hepatitis B can persist by taking advantage of suppressor cells in the liver that starve immune responses to ‘silence them’. Senior author, Professor Mala Maini (UCL Infection & Immunity), explained: “Our work has shown that during this ‘silent phase’ of infection, specialised suppressor cells switch off the immune response by cutting off its food supply. This is one of the many ways the liver protects itself from inflammation and immune damage but at the same time, prevents elimination of pathogens like hepatitis B.
“If we could boost the immune system and counteract the liver’s suppressive effect, then the infection could potentially be cleared after a large ‘burst’ of immune activity. This might cause short-term damage to the liver, but would prevent the long-term damage from scarring and liver cancers that we see in chronic patients.”
The team found that patients in the silent phases of infection had high levels of cells called granulocytic myeloid-derived suppressor cells (gMDSCs). These gMDSCs, which suppress T cells (immune cells) by cutting off their food supply, were found to accumulate in the liver
“The gMDSCs suppressed both the T cells that fight hepatitis B virus and those that cause inflammation in the liver,” commented lead author, Dr Laura Pallett (UCL Infection & Immunity). “Patients with more gMDSC tended to have less liver damage but were unable to control hepatitis B virus.”
These findings emphasise how nutrient supplies can regulate the immune system. They also suggest that suppressor cells such as gMSDC might have clinical uses in cases where the immune system attacks healthy tissue, such as autoimmune diseases or immune rejection of donated organs.
“If these cells can prevent immune cells from damaging the liver in hepatitis B patients, perhaps they could help to prevent immune rejection of transplanted livers,” said Professor Maini.
