A research team at the Mainz University Medical Center has discovered a previously unknown mechanism by which the immune system fights bacterial infections. The ion channel PACC1 plays a crucial role in the effective killing of bacteria by immune cells. If the protein is missing, there are increased inflammatory reactions and, in animal models, a significantly increased mortality rate from bacterial sepsis.

Sepsis, also known as blood poisoning, is the third most common cause of death in Germany. It occurs when the immune system can no longer locally limit an infection and faulty defensive reactions cause life-threatening damage to tissue and organs. Despite intensive medical treatment, about 20 to 50 percent of those affected die as a result.

The immune system fights bacterial pathogens with the help of phagolysosomes – specialized cell compartments in which bacteria are broken down. This degradation requires an acidic environment, which is regulated by ion channels in the membrane of the compartments. The exact mechanism of action of these channels in the immune defense was largely unclear until now.

The research group led by Prof. Dr. Markus Bosmann from the Center for Thrombosis and Hemostasis (CTH) at the Mainz University Medical Center has now shown that the proton-activated chloride channel 1 (PACC1) plays a central protective role in life-threatening bacterial infections. Without PACC1, the immune cells are no longer sufficiently successful in fighting bacteria. The digestive chambers do not remain sufficiently acidic, so that the bacteria are less well broken down. This leads to an increased and misdirected inflammatory response.

In the animal model, mortality from bacterial sepsis increased significantly. In pure inflammatory reactions without living bacteria, these effects did not occur. This underlines the specific importance of PACC1 for bacterial defense.

The results, published in the journal “Proceedings of the National Academy of Sciences” (PNAS), provide clues as to how disturbances in the bacterial defense can contribute to the development of serious infections such as sepsis. In the long term, they could open up new approaches to therapies – especially against the backdrop of rising antibiotic resistance. In the future, a targeted increase in PACC1 activity could serve as a mode of action for novel treatments against bacterial sepsis.

The study is titled “Proton-Activated Chloride Channel 1 (PACC1) is essential for innate host defense against bacterial sepsis”.

Original Paper:

Proton-activated chloride channel 1 is essential for innate host defense against bacterial sepsis | PNAS

Editor: X-Press Journalistenbüro GbR

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