Fighting Bacteria Without Antibiotics

About 170,000 people die each year from complications of hepatic cirrhosis in Europe. This widespread disease is caused by alcohol abuse, fatty liver hepatitis and chronic viral hepatitis, with liver cirrhosis developing gradually over a period of years and decades. These cells die and then get replaced by connective tissue. The flow of blood through the liver is blocked by scar tissue, leading to increased pressure in the blood vessels in the intestine, and leads to the leakage of intestinal bacteria that will reach the liver by the blood.

Bacterial infections make up about 1/3 of the fatal cases of hepatic cirrhosis, according to Prof. Dr. Jonel Trebicka from the Department of Internal Medicine in the University Hospital Bonn, who is participating in the study and has been studying liver cirrhosis for many years. Mice suffering from liver cirrhosis were observed and sustained production of Type-1 interferon in response to the intestinal bacteria by immune cells responsible for defense against infection. These are namely macrophages and monocytes in the liver. When infected by a small number of the pathogenic bacteria, Listeria, the production of Type-1 interferon massively increased. Consequently, the immune-regulatory factor interleukin-10 was released, leading to a defect in the anti-bacterial functions of the macrophages and then to a fatal course of infections.

Dr. Zeinab Abdullah, a group leader at the Institute for Experimental Immunology in the University hospital Bonn, said “following infection with pathogenic bacteria, we also observed highly elevated production of Type-1 interferon and interleukin-10 by monocytes from cirrhosis patients”. These results identify the blind spot of the immune system that is responsible for the failure of the immune response to bacterial infections.

Experiments with mice revealed they are unable to produce Type-1 interferon and were protected against Listeria infection despite the migration of the gut bacteria in to the liver, because their immune cells didn’t produce high levels of Type-1 interferon and IL-10 after Listeria infection. This reveals that we might now be able to treat a life-threatening bacterial infection without antibiotics, just by strengthening the immune response.

There is a prospect of reinvigorating the immune system, when the formation of Type-1 interferon in the liver cells is blocked by suitable substances. Further clinical studies must be performed, even though this looks like a very promising approach.
-Dr Fredda Branyon