For a fast response to disease-causing bacteria are macrophages, scavenger cells, of vital importance. Macrophages take up the bacteria via phagocytosis and kill them with digesting enzymes. However, some bacteria species like Listeria monocytogenes are specialized in avoiding being killed by the macrophages and instead use these cells for proliferation and spreading in the body.
„We were able to show a new mechanism playing an important role in killing the listeria. It is a special form of phagocytosis where the fate of the host and the intruder is decided early,” Michael Schramm, last author of the paper explains. Characteristic for this special form of phagocytosis is a cytoplasmatic protein called microtubule-associated protein 1/light chain 3B (short: LC3). “As we could show, the presence of LC3 fosters the fusion of vesicles containing the listeria with lysosomes, which are vesicles containing digestion enzymes. This expedited transfer of lysosomal enzymes into the phagosome is crucial for effective killing of the listeria,” says Michael Schramm.
A genetic defect regarding LC3-associated phagocytosis leads to better survival of the listeria in macrophages and therefore to an uncontrolled proliferation of the bacteria and spreading of the infection. How the macrophages use the LC3-associated phagocytosis against listeria could also be shown by the working group. A specific cell surface molecule, the ß2 integrin Mac-1, is responsible for the participation of LC3 in phagocytosis. With a complex chain of signals, Mac-1 takes care that listeria are exposed to reactive oxygen species. These reactive oxygen radicals help in two respects killing the listeria: They can directly harm the listeria and they improve recruitment of LC3 to the phagosome – leading to increased fusion with lysosomes and transfer of digesting enzymes.
“Our research identified LC3-associated phagocytosis as an important mechanism of anti-listerial immunity as macrophages employ it to restrict the proliferation of listeria and prevent an uncontrolled infection of the whole organism. In light of the worrying tempo of growing resistance to antibiotics, such findings on the defense mechanisms of our immune systems are key for the development of innovative therapies against bacterial infections,” Schramm adds.
The β2 Integrin Mac-1 Induces Protective LC3-Associated Phagocytosis of Listeria monocytogenes
Alexander Gluschko, Marc Herb, Katja Wiegmann, Oleg Krut, Wolfram F. Neiss, Olaf Utermöhlen, Martin Krönke, Michael Schramm
Cell Host & Microbe 23 (2018) pp. 324-337
Dr. Michael Schramm
Junior Group Leader, Institute for Medical Microbiology, Immunology and Hygiene