Wir überwinden Grenzen

The immune system is often faced with the challenge of having to protect the organism from various pathogens at the same time. Researchers at the Institute of Immunology at the Freiburg University Medical Center have now deciphered why this can be a problem in mice. In a study funded by the German Research Foundation, they discovered how an immune response directed against a virus is inhibited by a simultaneous bacterial infection. The researchers identified the bacterial component and the cellular interactions that are responsible for this surprising effect. In the long term, the findings could provide a new starting point for better treatment of dual infections. They published their findings on October 8, 2018 in the journal Nature Communications.

A viral infection actually activates T cells of the immune system in the body. These can specifically fight the virus. "We found that a concurrent bacterial infection strongly inhibits the activation of T cells. This prevents effective defense against the virus," says study leader Prof. Dr. Hanspeter Pircher, Director of the Institute of Immunology at the Freiburg University Medical Center.

"This mechanism could serve to inhibit an excessive immune response and thus prevent tissue damage caused by immune cells. However, the processes could also be described as a kind of 'friendly fire' in the immunological defense battle."

Immune cells destroy each other

The researchers proved that a component of some bacteria, the lipopolysaccharide LPS, is responsible for this inhibition. However, the LPS does not directly inhibit the T cells. Instead, it activates other immune cells, the natural killer cells (NK cells). NK cells are part of the innate immune system and are primarily responsible for controlling herpes viruses and malignant cells.

The Freiburg researchers have now been able to show that these natural killer cells destroy the T cells and thus weaken the virus defense. In the experiment, the scientists specifically switched off the natural killer cells. As a result, the T cells remained active and successfully fought the viral infection.

"Natural killer cells, which are activated by bacteria or other pathogens, inhibit the immune response against the virus through cell-damaging mechanisms," summarizes Prof. Pircher. This surprising finding illustrates the complex immunological networks that are important in the control of infectious pathogens. The study was carried out as part of the Collaborative Research Center 1160 "Immune-mediated pathology as a consequence of impaired immune reactions (IMPATH)".

Original title of the publication: Bacterial coinfection restrains antiviral CD8 T-cell response via LPS-induced inhibitory NK cells

DOI: 10.1038/s41467-018-06609-z

Link to the study: www.nature.com/articles/s41467-018-06609-z (Open Access)

Further information:

Institute of Immunology, Freiburg University Medical Center

Contact: 
Prof. Dr. Hanspeter Pircher 
Director 
Institute of Immunology 
Phone: 0761 203-6521 
hanspeter.pircher@uniklinik-freiburg.de