Neutrophils respond to infection by releasing chromatin in the form of neutrophil extracellular traps (NETs). A detailed understanding of this phenomenon eluded scientists until recently when new research revealed how NETs, or DNA snares, are released and how they stop a fungus from establishing an infection in mice and human cells.
"This is basically a type of beneficial cell suicide," says Borko Amulic, a postdoc in the lab of Arturo Zychlinsky at the Max Planck Institute for Infection Biology as well as newly appointed lecturer at the University of Bristol, and first author on the recent paper in Developmental Cell. "When neutrophils get overwhelmed, when they can no longer deal with a microbial threat by just engulfing it, that's when the NETs are released."
Once a neutrophil is forced to release its NETs, it anchors itself in the tissue and breaks down its nuclear envelope: the barrier between the nuclear DNA and the rest of the cell. Normally, cells only break down their nuclear envelope before they divide, so Zychlinsky, Amulic, and colleagues hypothesized that neutrophils were using the same cell cycle proteins used for cell division to release the NETs.
To test this, the team inhibited the cell cycle proteins in mouse neutrophils so that fewer NETs were released and found that mice were no longer able to clear fungal infections. Then, they observed human brains with fungal infections and confirmed that our neutrophils are also using cell cycle proteins.
"The ultimate goal for this research is to interfere clinically, either when too few or too many NETs are being produced," says Amulic.
Image: Bacteria (Shigella flexneri) trapped in a NET. The mesh-like structure of the NET is visible between two still-intact neutrophils. Image courtesy of Volker Brinkmann.