Immune reactions New signaling pathway with influence on inflammatory processes discovered

Researchers identify previously unknown signaling pathway of the human immune response
The immune response of the human organism is crucial to ward off pathogens and maintain good health, but it can also get out of hand and initiate chronic inflammatory processes. Scientists at the Ludwig Maximilian University (LMU) in Munich have now discovered a previously unknown signaling pathway that has a significant impact on the body's immune response. "We call this signaling pathway the alternative inflammasome, in order to distinguish it clearly from the previously described signaling pathways," explains study leader Veit Hornung, holder of the chair of immunobiochemistry at the Gene Center of the LMU.

According to the researchers, the discovered alternative signaling pathway could play a crucial role in inflammatory processes that occur, for example, in diseases such as gout, type 2 diabetes or arteriosclerosis. It also allows a particularly fast response of the immune system 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 needed as a messenger for a quick start of the immune reaction, according to the LMU. According to the researchers, the inflammasome NLRP3 is of crucial importance here. The scientists have published the results of their latest study in the journal "Immunity".

LMU scientists have identified a hitherto unknown immune-signaling pathway. (Image: psdesign1 / fotolia.com)

Quick start of the immune reaction
By combining new methods of investigation, the team led by LMU gene researcher Veit Hornung has identified "previously unknown molecular mechanisms in the human immune response," according to the University. Basically, the immune system distinguishes between "self" and "foreign" to repel pathogens or even cancer cells. However, the effective fight against "foreign" requires a quick start of the immune reaction, in which innate receptors of immune cells recognize foreign surface molecules, reports the LMU. Here, messenger substances are released, which bring the immune response in motion. The research team led by Veit Hornung was able to determine the signal pathway by combining two new methods, which enables this rapid start of the immune response.

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

The study is another example of the fact that results from the mouse model can not always be transferred one-to-one to humans, explain the researchers. Thus, only human monocytes in response to lipopolysaccharide would directly elicit the release of interleukin 1 without the need for a second stimulus. "Our results refute previous assumptions of inflammasome research. We hope that our new method can further contribute to understanding the cell biological foundations of immune diseases, "concludes Hornung and colleagues. (Fp)