Humans fight disease, bacteria and viruses constantly by invoking the immune system to destroy foreign particles in the body. Illnesses like human immunodeficiency virus (HIV), lupus and multiple sclerosis result from complications that inhibit the immune system response and, sometimes, cause the body to destroy its own tissues.
Researchers at the La Jolla Institute for Allergy and Immunology (LIAI) recently identified a process of the immune system that suppresses the body’s defense against chronic viruses. This “switchpoint,” as referred to by Matthias G. von Herrath, the principal investigator on the project, may lead to future treatment and therapy options for patients with viruses such as hepatitis C and HIV.
In a paper published in the Oct. 9 issue of The Journal of Experimental Medicine (JEM), von Herrath and researchers from his lab describe the function of a molecule called IL-10. It had been known as an immune messenger for almost 20 years when the group inadvertently identified it as a molecule produced in response to a chronic viral infection. Mette Ejrnaes, a student in von Herrath’s lab, suggested that the group study IL-10 in a chronic immune response to infection. The virus chosen for study was lymphocytic choriomeningitis (LCMV) in its natural host, the common mouse.
When the body is infected with a virus, the immune system invokes a defense response to fight the virus. Sometimes, that immune response is so strong that it actually harms the body. In this study, results suggest that IL-10 suppresses the immune response against viral infection and leaves the body susceptible to harm from the virus. Although this prevents the immune response from harming the body, it does not allow the body to fight the infection. The body is then susceptible to harm from the virus.
“The key is to re-educate the immune system,” said Christophe M. Filippi, a primary author on the paper published in JEM and researcher on the study.
He explained IL-10 production as a malfunction of the immune system.
“It (the immune system) can, at times, not act in a fashion that is actually beneficial to us as a living organism,” he said.
When these researchers blocked the production of IL-10 in mice chronically infected with LCMV, they discovered that the mice could clear the virus from their bodies and recover to be healthy again. Von Herrath said, “… the fact that it works so stunningly well — when you block the receptor of the immune response [thereby blocking IL-10 productions] that the virus gets eliminated is very reasonable.”
The next step would be to test the viral immune response of in-vitro human cells exposed to hepatitis C viral infection. The hepatitis C virus also invokes IL-10 production in response to a chronic viral attack but is not testable in the common mouse the way LCMV is tested. Hepatitis C is a worldwide cause of disease and cancer, and, therefore, an understanding of its function in the body is very important.
To be effective, von Herrath explained that the immune system should be activated enough to fight a chronic virus but not activated so much as to cause damage to the body’s own tissues.
“Get rid of the virus, don’t do too much damage, ” he said.
He further explained that if the research continues to produce promising results in the lab in human cells, it would be brought into clinical trials as a treatment for humans.
“[For best results] this treatment would be mixed with a vaccine,” he said.
Filippi described the effective treatment of IL-10 suppression as one that would “wake up the immune system and order it to fight infection.”
Von Herrath and all of the primary researchers on this project (Ejrnaes, Filippi and Marianne M. Martinic) have high hopes for the successful future of a new immune therapy.
“Let’s keep our fingers crossed … that this will translate in animal models and human situations … and that this is one that can result in a new therapy,” von Herrath said.