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USC researchers discover potential cure for chronic hepatitis B
https://news.usc.edu/99456/mothers-hepatitis-b-supports-chronic-infection-in-children-study-finds/
Chronic hepatitis B infection, a lifetime disease with no effective cure, could one day be cleared from a person’s system with a series of shots, according to a new USC study.
Most healthy adults infected with HBV will develop protective immunity, healing their own bodies within a few months. But children who acquired the virus from their mothers are unable to scrub HBV from their systems. Instead these individuals are fated to live with the virus for the rest of their lives.
About 1.1 million people in the United States have chronic HBV infection, the Centers for Disease Control and Prevention reported in 2013. USC is devoted to attacking today’s “wicked problems,” which include infectious diseases.
“Hepatic macrophages” — liver immune cells that eliminate foreign substances and toxins like a garbage disposal system — could be the target of future treatment, said Jing-hsiung James Ou, a professor of molecular microbiology and immunology at the Keck School of Medicine of USC.
“Maternal viral antigens teach the offspring’s hepatic macrophages to suppress foot soldier white blood cells called CTLs,” said Ou, senior author of the article published May 3 in Immunity, a Cell journal. “Therefore, when babies are exposed to the virus, the baby’s ‘garbage disposal units’ will suppress its own immune system from fighting off the infection. We were able to deplete macrophages in a mouse model, activate CTLs and clear the virus.”
A path toward a cure?
The study paves a path to curing chronic HBV infection, Ou said. His research unveils the function of HBV e antigen, which was previously a mystery, Ou added.
In a mouse model, the experimental group came from mothers with HBV, whereas the control group came from mothers without HBV. Scientists introduced HBV-inducing DNA into offspring mouse liver to produce HBV.
Measurements taken throughout the 28-week experiment found that the test group’s hepatic macrophages turned against their foot soldier CTLs. In other words, white blood cells in the offspring of HBV-positive mice were weakened because of renegades within the ranks.
To remove macrophages that prevented the immune system from eliminating HBV infection, Ou and his colleagues injected the test group with a drug that slays these traitors. Researchers performed the procedure two days before and once every five days after HBV DNA was administered. In total, researchers dispensed the drugs four times.
In the future, clinical treatment for chronic HBV infection may last merely one month rather than a lifetime.
James Ou
The drug removed macrophages and restored normal CTL white blood cell activity, leading to HBV clearance after about four weeks. Ou said he will further his research in animal studies, which is essential to ensure the safety of the drug before the initiation of clinical trials.
“This study opens doors,” he said. “In the future, clinical treatment for chronic HBV infection may last merely one month rather than a lifetime.”
The study was supported by National Institutes of Health grants (DK100257 and CA177337) and a research grant from the L.K. Whittier Foundation.
Chronic hepatitis B infection, a lifetime disease with no effective cure, could one day be cleared from a person’s system with a series of shots, according to a new USC study.
Most healthy adults infected with HBV will develop protective immunity, healing their own bodies within a few months. But children who acquired the virus from their mothers are unable to scrub HBV from their systems. Instead these individuals are fated to live with the virus for the rest of their lives.
About 1.1 million people in the United States have chronic HBV infection, the Centers for Disease Control and Prevention reported in 2013. USC is devoted to attacking today’s “wicked problems,” which include infectious diseases.
“Hepatic macrophages” — liver immune cells that eliminate foreign substances and toxins like a garbage disposal system — could be the target of future treatment, said Jing-hsiung James Ou, a professor of molecular microbiology and immunology at the Keck School of Medicine of USC.
“Maternal viral antigens teach the offspring’s hepatic macrophages to suppress foot soldier white blood cells called CTLs,” said Ou, senior author of the article published May 3 in Immunity, a Cell journal. “Therefore, when babies are exposed to the virus, the baby’s ‘garbage disposal units’ will suppress its own immune system from fighting off the infection. We were able to deplete macrophages in a mouse model, activate CTLs and clear the virus.”
A path toward a cure?
The study paves a path to curing chronic HBV infection, Ou said. His research unveils the function of HBV e antigen, which was previously a mystery, Ou added.
In a mouse model, the experimental group came from mothers with HBV, whereas the control group came from mothers without HBV. Scientists introduced HBV-inducing DNA into offspring mouse liver to produce HBV.
Measurements taken throughout the 28-week experiment found that the test group’s hepatic macrophages turned against their foot soldier CTLs. In other words, white blood cells in the offspring of HBV-positive mice were weakened because of renegades within the ranks.
To remove macrophages that prevented the immune system from eliminating HBV infection, Ou and his colleagues injected the test group with a drug that slays these traitors. Researchers performed the procedure two days before and once every five days after HBV DNA was administered. In total, researchers dispensed the drugs four times.
In the future, clinical treatment for chronic HBV infection may last merely one month rather than a lifetime.
James Ou
The drug removed macrophages and restored normal CTL white blood cell activity, leading to HBV clearance after about four weeks. Ou said he will further his research in animal studies, which is essential to ensure the safety of the drug before the initiation of clinical trials.
“This study opens doors,” he said. “In the future, clinical treatment for chronic HBV infection may last merely one month rather than a lifetime.”
The study was supported by National Institutes of Health grants (DK100257 and CA177337) and a research grant from the L.K. Whittier Foundation.
i had a look to the liposomal drug, interesting but of course extremely dangerous, i think only researchers with experience with bone marrow or transplant may have the experience to suppress immune system like this without death dangers
i have little time lately to check these studies, are we sure this leads to hbv clearance?
i have little time lately to check these studies, are we sure this leads to hbv clearance?
There is also another paper related to macrophages:
Interferon-γ facilitates hepatic antiviral T cell retention for the maintenance of liver-induced systemic tolerance
Zhutian Zeng,1,* Lu Li,1,2,* Yongyan Chen,1 Haiming Wei,1 Rui Sun,1 and Zhigang Tian1,2,3
1Institute of Immunology and the Key Laboratory of Innate Immunity and Chronic Disease, Chinese Academy of Science, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China
2Hefei National Laboratory for Physical Sciences at the Microscale, Hefei 230027, China
3Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
Correspondence to Zhigang Tian: tzg{at}ustc.edu.cn
↵* Z. Zeng and L. Li contributed equally to this paper.
Abstract
Persistent exposure to liver pathogens leads to systemic antigen-specific tolerance, a major cause of chronicity during hepatotropic infection. The mechanism regarding how this systemic tolerance is maintained remains poorly elucidated. In a well established mouse model of hepatitis B virus (HBV) persistence–induced systemic tolerance, we observed that interferon-γ (IFN-γ) deficiency led to complete loss of tolerance, resulting in robust anti-HBV responses upon peripheral vaccination. The recovery of vaccine-induced anti-HBV responses was mainly caused by the retained antigen-specific CD4+ T cells rather than decreased functional inhibitory cells in the periphery. Mechanistically, HBV persistence induced sustained hepatic CD4+ T cell–derived IFN-γ production. IFN-γ was found to promote CXCL9 secretion from liver-resident macrophages. This T cell chemokine facilitated the retention of antiviral CD4+ T cells in the liver in a CXCR3-dependent manner. Hepatic sequestrated antiviral CD4+ T cells subsequently underwent local apoptotic elimination partially via cytotoxic T lymphocyte–associated protein 4 ligation. These findings reveal an unexpected tolerogenic role for IFN-γ during viral persistence in the liver, providing new mechanistic insights regarding the maintenance of systemic antigen-specific tolerance during HBV persistence.
Members of the Chinese forum have identified an existing drug that causes apoptosis of macrophages. Given the importance of macrophages as immune cells and its variety, it would be interesting to see how treatment targeting macrophages would pan out.
Interferon-γ facilitates hepatic antiviral T cell retention for the maintenance of liver-induced systemic tolerance
Zhutian Zeng,1,* Lu Li,1,2,* Yongyan Chen,1 Haiming Wei,1 Rui Sun,1 and Zhigang Tian1,2,3
1Institute of Immunology and the Key Laboratory of Innate Immunity and Chronic Disease, Chinese Academy of Science, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China
2Hefei National Laboratory for Physical Sciences at the Microscale, Hefei 230027, China
3Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
Correspondence to Zhigang Tian: tzg{at}ustc.edu.cn
↵* Z. Zeng and L. Li contributed equally to this paper.
Abstract
Persistent exposure to liver pathogens leads to systemic antigen-specific tolerance, a major cause of chronicity during hepatotropic infection. The mechanism regarding how this systemic tolerance is maintained remains poorly elucidated. In a well established mouse model of hepatitis B virus (HBV) persistence–induced systemic tolerance, we observed that interferon-γ (IFN-γ) deficiency led to complete loss of tolerance, resulting in robust anti-HBV responses upon peripheral vaccination. The recovery of vaccine-induced anti-HBV responses was mainly caused by the retained antigen-specific CD4+ T cells rather than decreased functional inhibitory cells in the periphery. Mechanistically, HBV persistence induced sustained hepatic CD4+ T cell–derived IFN-γ production. IFN-γ was found to promote CXCL9 secretion from liver-resident macrophages. This T cell chemokine facilitated the retention of antiviral CD4+ T cells in the liver in a CXCR3-dependent manner. Hepatic sequestrated antiviral CD4+ T cells subsequently underwent local apoptotic elimination partially via cytotoxic T lymphocyte–associated protein 4 ligation. These findings reveal an unexpected tolerogenic role for IFN-γ during viral persistence in the liver, providing new mechanistic insights regarding the maintenance of systemic antigen-specific tolerance during HBV persistence.
Members of the Chinese forum have identified an existing drug that causes apoptosis of macrophages. Given the importance of macrophages as immune cells and its variety, it would be interesting to see how treatment targeting macrophages would pan out.
oh my extremely generic words, we should see the study directly
i guess they refer to M2 macrophages only?and their suppression only?
i guess they refer to M2 macrophages only?and their suppression only?
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