Immune reactions: new signaling pathway with influence on inflammatory processes discovered

Immune reactions: new signaling pathway with influence on inflammatory processes discovered

Researchers identify previously unknown signaling pathways in the human immune response
The immune response of the human organism is crucial for the defense against pathogens and the maintenance of health, but it can also get out of hand and initiate chronic inflammatory processes. Scientists at the Ludwig Maximillians University (LMU) in Munich have now discovered a previously unknown signal path that has a significant impact on the immune response of the body. "We call this signaling pathway the alternative inflammasome in order to clearly differentiate it from the signaling pathways described so far," explains study leader Veit Hornung, holder of the chair for immunobiochemistry at the gene center of the LMU.

According to the researchers, the alternative signaling pathway discovered could play a decisive role in inflammatory processes that occur, for example, in diseases such as gout, type 2 diabetes or arteriosclerosis. It also enables the immune system to respond particularly quickly to foreign substances. Using a special procedure, the research team was able to "analyze unprecedented precision in how interleukin 1 is released by human cells", which is required as a messenger substance for a quick start of the immune response, according to the LMU. The inflammasome NLRP3 is of crucial importance here, according to the researchers. The scientists published the results of their current study in the specialist magazine "Immunity".

Quick start of the immune response
Through a combination of new investigation methods, the team led by LMU geneticist Veit Hornung has identified "previously unknown molecular mechanisms in the human immune response", according to the university. Basically, the immune system differentiates between "itself" and "foreign" to ward off pathogens or cancer cells. In order to effectively combat "foreign", however, a quick start of the immune response is required, in which innate receptors of immune cells recognize foreign surface molecules, reports the LMU. This releases messenger substances that trigger the immune response. The research team led by Veit Hornung was able to determine the signaling pathway that enables this quick start of the immune response by combining two new methods.

Mouse cells and human cells with different reactions
"By systematically switching off individual genes in a new type of cell that closely resembles human immune cells, it has been possible to uncover a previously unknown signal path that plays an important role in controlling inflammatory processes," the LMU said. Veit Hornung and his team had first dealt with the so-called NLRP3 inflammasome at the University Hospital Bonn, then at the LMU, to which Hornung switched in October 2015, which plays a key role in frequently occurring inflammatory diseases such as gout, type 2 diabetes or atherosclerosis. However, the studies on human cells showed different results than the previous analyzes, which were mainly based on experiments on mouse cells, reports the LMU. The mouse cells needed two initial stimuli for the NLRP3 inflammasome to release the messenger substance interleukin 1. However, human cells (monocytes) release this important messenger in response to a single stimulus.

The study is another example of the fact that results from the mouse model cannot always be transferred one to one to humans, the researchers explain. Only human monocytes in response to lipopolysaccharide would trigger the release of interleukin 1 directly, without the need for a second stimulus. “Our results contradict previous assumptions made by inflammasome research. We hope that our new method can further help to understand the cell-biological basis of immune diseases, ”concluded Hornung and colleagues. (fp)

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