Mast Cells Recruit Neutrophils in Immune Response

Mast cells are well-known for their part in allergic reactions, but the immune system relies heavily on them. They release chemicals in response to allergens, which cause common allergy symptoms like tissue swelling and inflammation.​​​​​​

Mast cells have a secret ability that researchers at the University of Münster and the Max Planck Institute of Immunobiology and Epigenetics in Freiburg have now identified: they can attract and utilize neutrophils, a different kind of immune cell. This unexpected finding provides fresh insight into the functioning of the immune system, especially concerning allergic reactions.

The body's reaction to damaging stimuli is called inflammation, which is characterized by heat, pain, redness, swelling, and a loss of tissue function. When inflammation is in balance, the body is shielded from harmful agents and begins tissue repair.

On the other hand, illness and tissue damage can result from excessive inflammation. Numerous immune cells are important participants in this process; they cooperate during inflammation. Depending on the harmful stimulus, different immune cell types are frequently involved, affecting the inflammation response.

Immune Cell Trapping During Allergic Responses

Granules containing pro-inflammatory substances are found inside mast cells, which are tissue-resident cells that are crucial in initiating inflammation. When possible threats, such as allergens, are encountered, these granules are released, which can result in allergic reactions.

Many people also have mast cell reactions to seemingly innocuous environmental stimuli, which serve as allergens and induce allergic reactions. Most of the research on the relationship between mast cells and other immune cells at the sites of allergic responses has not been done.

Activated mast cells and other cell types during allergic reactions in living mouse tissues were visualized in real-time using specialized microscopy by a research team at the MPI of Immunobiology and Epigenetics.

Under the direction of Tim Lämmermann, who has been the Director of the Institute of Medical Biochemistry at the University of Münster since October 2023, the team found an unexpected interaction: mast cells contained neutrophils.

We could hardly believe our eyes: living neutrophils were sitting inside living mast cells. This phenomenon was completely unexpected and probably would not have been discovered in experiments outside a living organism and highlights the power of intravital microscopy.”

Tim Lämmermann, Director, Institute of Medical Biochemistry, University of Münster

Pulling a Neutrophil Trick to Trap Neutrophils

The immune system’s front-line protectors, neutrophils, react swiftly and extensively to possible threats. They swiftly leave blood vessels at inflammatory sites and circulate throughout the body. Their arsenal of defense mechanisms includes engulfing intruders like bacteria or fungi, secreting antimicrobial agents, and creating web-like structures called neutrophil extracellular traps.

Furthermore, neutrophils can coordinate their distinct roles for the defense of healthy tissue by forming cell swarms and communicating with one another. Although the function of neutrophils in infections and sterile injuries is well established, little is known about how they contribute to allergic reaction-induced inflammation.

It quickly became clear that the double-pack immune cells were no mere coincidence. We wanted to understand how mast cells trap their colleagues and why they do it.”

Michael Mihlan, Study First and Co-Corresponding Author, University of Münster

The study was published in the journal Cell.

Once they could replicate the neutrophil trapping seen in living tissue in cell culture, the scientists were able to determine the molecular pathways involved in this process. The researchers discovered that leukotriene B4, which neutrophils frequently use to start their swarming behavior, is released by mast cells.

Neutrophils are drawn to mast cells by the material they secrete. The term "mast cell intracellular trap" (MIT) refers to the cell-in-cell structure formed when mast cells engulf neutrophils into a vacuole once they are sufficiently close.

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.”

Tim Lämmermann, Director, Institute of Medical Biochemistry, University of Münster

Recycled Neutrophils to Boost Mast Cell Function

The researchers examined the fate of the two cell types involved after trapping and verified the formation of MITs in human samples with the assistance of an international team. It was discovered that the dead bodies of trapped neutrophils are eventually stored inside mast cells.

Michael Mihlan said, “This is where the story takes an unexpected turn. Mast cells can recycle the material from the neutrophils to boost their 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 defense.”

“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 capabilities – an aspect that could have implications for chronic allergic conditions where inflammation occurs repeatedly,” said Tim Lämmermann.

Researchers have already started investigating mast cell-mediated inflammatory diseases in humans to determine whether this interaction could result in novel treatments for allergies and inflammatory illnesses.