Researchers have elucidated the link between chronic liver disease and a high susceptibility to viral infections. The findings help to restore the immune response to vaccinations and better protect patients.
Chronic liver diseases (CLD) – how liver cirrhosis and fibrosis – have various effects that go beyond direct liver functions: Patients have an increased susceptibility to viral infections, which are often incurable and can lead to life-threatening diseases. In addition, CLD patients show a weak response vaccinations.
Both could indicate a restricted functionality of the adaptive immune system be due to: The loss of T cell immunity in CDL patients is a known clinical complication. To the functionality of their immune system it is important to understand the mechanisms underlying the loss of T-cell immunity during liver injury.
mechanisms identified
Chronic liver diseases are often caused by a pathological change in the Darmflora accompanied, so that intestinalMicrobiota into the bloodstream and ultimately into the liver. There they activated the immune cells in the liver and induced the release of Interferon Type I (IFN-I): An alarm signal for surrounding immune cells in the liver. “The alarmed innate immune cells in turn set off another anti-inflammatory cytokine On behalf of Interleukin 10 free,” explains immunologist Prof. Zeinab Abdullah. “We have identified interleukin 10 as the key mediator of disrupted T cell functionality in CDL.”
suppressed immune response
“When we examined the virus-specific T cells in the context of CDL, we observed the same gene signature as in depleted, dysfunctional T cells in cancer and chronic viral infections,” says researcher Dr. Suzanne Schmidt. A hallmark of these defective T cells is the upregulation of genes induced by the anti-inflammatory cytokine interleukin 10 (IL-10). These T cells are then no longer able to carry out their part of the immune response.
Blockage saves T cells
The researchers were able to show that specific neutralization of IFN-I and IL-10 leads to the restoration of T cell immunity against viral infections. “We identified the IL-10 signaling pathway as a potential target to restore the T cell-mediated immune response and also the efficacy of vaccination in CLD patients,” explains Abdullah. To recognize IL-10 in their environment, T cells use an IL-10 receptor on their surface. By specifically blocking this receptor, the scientists were able to restore antiviral immunity in mice.
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This finding was confirmed in vaccinated cirrhotic patients. In addition, the treatment showed no immunopathological side effects, making IL-10 signaling a promising target for restoring T cell immunity in CLD patients. “Our study underscores the fundamental role of the microbiota and the gut-liver axis in suppressing antiviral immune functions. This applies not only to patients suffering from CDL, but also to the systemic persistence of viral infections and poor response to vaccination,” concludes Abdulah.
This text is based on a press release of the University Hospital Bonn. Here go to the original publication.
Image source: Andrea De Santis, unsplash