When the hunters become the hunted
Braunschweig Helmholtz researchers show how bacteria drive immune cells to death
The immune system defends the body against pathogens. Macrophages are part of the first line of defence: they identify pathogens that have gained entry and destroy them. Bacteria that infiltrate the body are not powerless to resist the macrophages, however. Substances formed by the bacteria attack the macrophages, an attack that they sometimes fail to survive.
Eva Medina and her Infection Immunology research group at the Helmholtz Centre for
Infection research (HZI) in Braunschweig have discovered a new mechanism that leads to the destruction of macrophages. The results have been published in the current issue of the scientific journal Cellular Microbiology.
Macrophages identify bacteria, fungi and viruses that can make the body ill. They
absorb these germs in order to combat them. Inside the cell they destroy the intruders and use chemical messenger substances to draw further immune cells into the source of infection. If the macrophages are unable to defend themselves against the bacteria, then the bacteria gain the upper hand – the infection spreads.
Eva Medina and her research group at the HZI investigated the manner in which the bacteria
Streptococcus pyogenes attacks the macrophages. The findings came as a surprise to the researchers: the bacteria destroy the power plants of the macrophages, the mitochondria. As a result, energy supplies collapse and the cells die. In their experiments the researchers identified the previously unidentified mechanism that leads to the destruction of the mitochondria and subsequent cell death.
The process commences with substances produced by the bacteria that penetrate the cell walls of the macrophages. "Bacteria produce these so-called cytolysines continuously in order to prepare themselves for meeting our immune defence system," says Eva Medina. The researchers attempted to block the holes in the membrane of the macrophages and thereby save the cells. Although this proved successful, the cells died nevertheless. Medina's team identified the reason for this after some time: the bacteria had not only penetrated the cell wall, in the process they had also damaged the "cell power plants", the mitochondria. "Normally, the macrophages have learned to evade these cytolysines and neutralise them. However, the holes in the membrane trigger stress in the cells and also inhibit the mitochondria inside the cell. Finally, they give up and cease producing energy," says Medina.
That which results in death for the macrophages aids the bacteria in the infection. "The bacteria kill the macrophages insidiously from a distance. The body's first line of defence collapses. The cell death of the macrophages results in tissue damage and the bacteria are able to spread out more easily," says Medina. "By the time the immune system realises that something is wrong, it is too late."
Original article: Oliver Goldmann, Inka Sastalla, Melissa Wos-Oxley, Manfred Rohde and Eva Medina: Streptococcus pyogenes induces oncosis in macrophages through the activation of an inflammatory programmed cell death pathway, Cell Microbiol 2009, 11(1):138-155