Nav: Home

Hepatitis therapy: Kupffer cells adjust the balance between pathogen control and hepatocyte regenera

January 17, 2018

Hannover and Amsterdam, Jan. 17, 2018 - Inflammation of the liver can result from different causes. Besides infections with hepatitis B virus (HBV) and hepatitis C virus (HCV), other viruses such as cytomegalovirus (CMV) are able to trigger acute hepatitis. Sometimes hepatitis induces fever and flu-like symptoms, however, it may also damage the liver and might even result in acute liver failure. Yet, currently there is no general agreement on how acute hepatitis should be treated: Should the immune response against the viral pathogen be reinforced or inhibited? Scientists from TWINCORE have now published new insights on the processes involved in liver inflammation in the Journal of Hepatology: Type I interferons, on the one hand, limit viral replication and thereby help the immune cells to control the viral pathogen. On the other hand, type I interferons delay the regeneration of immune cells, which are important to adjust and maintain the immune balance within the liver during acute inflammation.

"So far, it has been assumed that viral replication itself destroys liver cells," says Katharina Borst, scientist at the Institute for Experimental Infection Research, TWINCORE, Hannover, Germany. "Meanwhile we also know that local inflammatory processes can damage the liver." This is critical knowledge, because, if the inflammatory reaction and not the virus accounts for liver damage, one should not enhance the inflammation within the already inflamed organ by treatment with an inflammatory cytokine such as type I interferon. "On the other hand, in clinical practice it is well established that type I interferon is an effective treatment during acute hepatitis and that it protects the liver," argues Dr. Theresa Frenz, also scientist at the Institute for Experimental Infection Research, TWINCORE. At first glance this is a paradoxical situation that needs clarification.

Therefore, the scientists set out to understand the mechanism by which type I interferon works in the liver. To understand the local immune responses, they analyzed Kupffer cells, which are liver-resident scavenger cells within the immune system. The researchers used vaccinia virus to infect livers that either could or could not detect type I interferon, or in which only the Kupffer cells or the hepatocytes, the main cell type of the liver, could or could not detect type I interferon.

"This experiment showed us that hepatocytes do not need type I interferon to combat viral infection, since we could not find differences, regardless of whether we analyzed normal livers or livers in which only hepatocytes did not detect type I interferon," says Katharina Borst. "This is surprising, since hepatocytes are the main target cell for type for infection."

However, type I interferon seems to be important for Kupffer cells, says Dr. Frenz: "We believe, that type I interferon triggers Kupffer cells to take up infected cells and undergo apoptosis (suicide) afterwards, since surprisingly, Kupffer cells disappear after infection." The body replaces those lost Kupffer cells by scavenger cells, which develop from the bone marrow. Such cells are not "real" Kupffer cells, but they still take over similar tasks. Interestingly, this process is accelerated if the bone marrow cells cannot sense type I interferon," says Ms. Borst. "Obviously, type I interferon is very important to adjust the regulation of inflammatory processes."

"We verified that therapeutic treatment of acute viral hepatitis with type I interferon is reasonable, since it activates local immune cells and helps to eliminate the virus," concludes institute director Prof. Ulrich Kalinke. "However, in order to better support the regeneration of the inflamed liver, we need to learn more about the balance of enhancement and modulation of inflammation. This will be the basis to develop new therapeutic interventions for acute hepatitis."
-end-


Elsevier

Related Hepatitis Articles:

Nanotechnology delivers hepatitis B vaccine
X-ray imaging shows that nanostructured silica acts as a protective vehicle to deliver intact antigen to the intestine so that it can trigger an immune response.
Checkmate for hepatitis B viruses in the liver
Researchers at Helmholtz Zentrum M√ľnchen and the Technical University of Munich, working in collaboration with researchers at the University Medical Center Hamburg-Eppendorf and the University Hospital Heidelberg, have for the first time succeeded in conquering a chronic infection with the hepatitis B virus in a mouse model.
How common is Hepatitis C infection in each US state?
Hepatitis C virus infection is a major cause of illness and death in the United States and injection drug use is likely fueling many new cases.
New strains of hepatitis C found in Africa
The largest population study of hepatitis C in Africa has found three new strains of the virus circulating in the general population in sub-Saharan Africa.
High stability of the hepatitis B virus
At room temperature, hepatitis B viruses (HBV) remain contagious for several weeks and they are even able to withstand temperatures of four degrees centigrade over the span of nine months.
Findings could lead to treatment of hepatitis B
Researchers have gained new insights into the virus that causes hepatitis B -- a life-threatening and incurable infection that afflicts more than 250 million people worldwide.
How to cure more hepatitis C patients
The cost of cures for hepatitis C have been prohibitive, but experts who served on an NAS panel have a solution that will save more patients and incentivize drug innovation.
Hepatitis C: A novel point-of-care assay
One of the major challenges identified by the WHO in efforts to eradicate the hepatitis C virus is the diagnosis of chronic cases that are generally asymptomatic.
Countries risk 'running out' of hepatitis C patients to treat, says World Hepatitis Alliance
The latest data on the global hepatitis C epidemic, released today at the World Hepatitis Summit in Sao Paulo, Brazil, reveal that most countries (especially high-income countries) are running out of patients to treat because of the low diagnosis rates worldwide.
Australia currently on track to eliminate hepatitis C by 2030, but challenges remain for hepatitis B
New data released at this year's World Hepatitis Summit in Sao Paulo, Brazil, shows that Australia is currently on track to eliminate hepatitis C thanks to its huge efforts to enable population-wide access to treatment.
More Hepatitis News and Hepatitis Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.