As if immune cells weren’t already weird enough, researchers studying allergic responses in mice have spotted something completely unexpected: immune cells nestled inside each other like Matryoshka dolls.
Lead researcher Tim Lämmermann, director of the Institute of Medical Biochemistry at the University of Münster, Germany, says the phenomenon was completely unexpected.
“We could hardly believe our eyes: living neutrophils were sitting inside living mast cells,” he says.
“This new understanding of how mast cells and neutrophils work together adds a whole new layer to our knowledge of allergic reactions and inflammation.
“It shows that mast cells can use neutrophils to boost their own capabilities – an aspect that could have implications for chronic allergic conditions where inflammation occurs repeatedly.”
Mast cells are a type of immune cell that live in tissues. They are critical for initiating inflammation, which they do by releasing granules containing pro-inflammatory substances upon encountering potential dangers, including allergens.
Neutrophils circulate in the blood but can quickly exit blood vessels at sites of inflammation. Once in tissues they engulf invading microbes, release antimicrobial substances, and forming web-like “neutrophil extracellular traps.”
Lämmermann’s team studied the real-time dynamics of activated mast cells and other cell types during allergic reactions in living mouse tissues using intravital microscopy.
“It is ironic that neutrophils, which create web-like traps made of DNA and histones to capture microbes during infections, are now trapped themselves by mast cells under allergic conditions,” says Lämmermann.
They found that mast cells release leukotriene B4, a substance commonly used by neutrophils to initiate their swarming behaviour, to attract neutrophils.
Once neutrophils come close enough, mast cells engulf them into membrane-bound organelles that the researchers refer to as a “mast cell intracellular traps” or MITs.
Human cell studies revealed the trapped neutrophils eventually die and their remains get stored inside mast cells.
“This is where the story takes an unexpected turn,” adds Michael Mihlan, first author of the study published in the journal Cell.
“Mast cells can recycle the material from the neutrophils to boost their own function and metabolism.
“In addition, mast cells can release the newly acquired neutrophil components in a delayed manner, triggering additional immune responses and helping to sustain inflammation and immune defence.”
The researchers have begun investigating this interaction in mast cell-mediated inflammatory diseases in humans to explore whether this discovery could lead to new approaches to treating allergies and inflammatory diseases.
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