Researchers at the University of Liverpool have discovered a new and important function of a toxin produced by pathogenic bacteria that can have significant consequences for future vaccine design.
Streptococcus pneumoniae (pneumococcal) is an important cause of life-threatening invasive diseases such as pneumonia, septicemia and meningitis and is responsible for more than one million deaths each year. The key to its disease-inducing success is the effect of a powerful toxin called pneumolysin, which works by creating "holes" in the membranes of human cells and either killing them directly or causing material damage to the tissue.
So far, researchers believed that the effects of pneumolysin resulted purely from the binding of the toxin to cholesterol in host cell membranes. A new study published in nature Microbiologyhowever, shows that pneumolysin can also bind directly to a host cell receptor on specialized immune cells to suppress the immune response.
The study was a collaboration between the bacterial pathogenesis and the immunity group at the University's Infection and Global Health Institute and the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet in Stockholm.
With the help of specialized in vitro experiments in human cells and in vivo studies in mice, the team has shown that pneumolysin can bind directly to a host cell receptor called Mannose Receptor C Type 1 (MRC-1) on immune cells, including macrophages and dendritic cells, which causes them to reduce their production of molecules that promote inflammation and protective immunity. Bacteria can then survive easier in the airways, as inflammation and immune cell activity are suppressed.
Professor Aras Kadioglu, who led the study in Liverpool, said: "This is really a key moment in our understanding of how the pneumococcus causes disease. First, because it breaks a long-lasting dogma that pneumolysin can only bind to cholesterol, really the identification of A host receptor for pneumolysin has been the sacred degree in the field for many decades, and secondly, as it changes our understanding of how the pneumococcal uses its toxin to manipulate and change our immune response to its advantage. I am very excited about the potential of these new results. "
Dr Daniel Neill, a common author, added: "Understanding how bacteria can promote infection through toxin production helps researchers to develop new ways to fight serious infectious diseases. Several vaccines in development contain detoxified pneumolysin and it is important to investigate further how recently The described receptor binding activity may affect the immune response caused by such vaccination. "