07 July 2016

Neutrophils weave a web

How Immune Cells Make a Trap Net for Bacteria

Kirill Stasevich, "Science and Life", based on the materials of Medicalexpress: Immune cells cast nets to save us from harm

Among the rich "weapons" arsenal that immune cells use against infections, there is a rather strange method of catching bacterial cells in the DNA network. Neutrophils use such networks – they not only float in the bloodstream, but also crawl out of the vessels themselves, actively moving through the intercellular space in the tissues.

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DNA strands trailing neutrophils

Neutrophils are among the first to encounter foreign particles, be it bacteria or something else, and literally eat them. Bacterial cells die from a variety of immune proteins, but neutrophils themselves also die, releasing new portions of antibacterial substances and at the same time sending chemical signals that attract other immune cells to the "battleground".

However, chemical signals and antibacterial enzymes are not everything. In 2004, an article was published in the journal Science, the authors of which described a trap net appearing at the site of neutrophil death. This grid, as it turned out, is made of DNA, hung with the same toxic proteins that kill bacteria.

As you know, there are two molecular scenarios of cell death: necrosis and apoptosis (if you don't go into details, necrosis is a common death due to some external "force majeure circumstances", and apoptosis is a regulated process that starts at the moment when the cell can no longer work properly and is forced to commit suicide, in order not to harm others). But for neutrophils, we had to come up with a third type – netosis (from the word net – network).

During netosis, special enzymes destroy histone proteins that keep DNA in a packed, compressed state. Due to the fact that the "clasps"-histones disappear, the DNA in the neutrophil nuclei straightens and literally breaks the nucleus, filling the cellular cytoplasm. Here bactericidal proteins sit on the DNA strands, after which the outer membrane is already destroyed, and a tangle of DNA with antibacterial proteins ends up in the external environment, where bacteria swim.

At first, researchers were engaged only in those processes that occur in one cell, that is, in one neutrophil. But in reality, the DNA network appears with the participation of many neutrophils, so the question arises how they interact with each other. Astrid Obermayer and her colleagues from the University of Salzburg managed to find out this: they observed human and mouse neutrophils, which were forced to netosis, using various microscopic methods; and to see what happened to the network, luminous fluorescent molecules were added to the cells, which bound to proteins on the DNA network.

In a report made at the annual conference of the Society for Experimental Biology, the authors of the work compared immune cells with spiders: just as a spider first attaches a thread of a web to some reliable substrate, so neutrophils first fix a DNA rope somewhere outside, and then crawl away. The DNA trailing behind the neutrophil dissolves, and, most importantly, other cells that stumble upon it also begin to "weave a network" – something like a chain reaction occurs. As a result, even a small number of cells can "weave" their DNA into a relatively large space.

From an evolutionary point of view, such a trap net is a rather ancient trick, and similar nets can be found even in invertebrates, for example, in crabs and mollusks. Bacterial evolution, of course, also does not stand still, and some bacteria have already learned to turn this DNA network against the immunity itself: for example, Staphylococcus aureus modifies its strands in such a way that they become toxic to macrophage cells that come here to help destroy the infection.

Portal "Eternal youth" http://vechnayamolodost.ru  07.07.2016

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