Long-lived Macrophages Vital For Enteric Neuron Survival

Certain macrophages in the intestines of mice can survive for quite some time, scientists at KU Leuven, Belgium, report. Most importantly, these long-lived macrophages were found to be vital for the survival of the nerve cells of the gastrointestinal tract. This sheds new light on neurodegenerative conditions of the intestine, but also of the brain.

Macrophages are specialised immune cells that destroy bacteria and other harmful organisms. They are white blood cells that clean up foreign substances by engulfing them.

Apart from this, macrophages themselves provide vital growth factors and support many tissues in the body, allowing them to function and develop properly. As such, these specialised immune cells are soldier and nourisher at the same time.

Their proper functioning is immensely important in the intestine, as they have to differentiate between harmful bacteria, harmless bacteria and nutritional components.

Long-lived Macrophages

Scientists assumed that macrophages in the intestine live for about three weeks at most in both mice and humans before being replaced by new cells. This study now shows that this is not entirely true, explains Professor Guy Boeckxstaens;

“We’ve discovered a small percentage of long-lived macrophages in mice. We marked certain macrophages and found that they still functioned after at least eight months. They can be found in very specific places in the intestine, particularly in close contact with nerve cells and blood vessels.”

Additionally, the small group of long-lived macrophages play a very important role in the gastrointestinal tract, adds Ph.D. student Sebastiaan De Schepper.

“If the long-lived macrophages don’t do their job properly, after only a few days, the mice suffer from digestive problems. This leads to constipation or even the complete degeneration of the nervous system in the stomach and intestine.”

The discovery that long-lived macrophages do, indeed, exist in the intestine and that they are crucial for the normal functioning of the intestine is therefore immensely important.

Intestinal Homeostasis

These new insights offer promising opportunities for further research:

“Next, we want to study the role of long-lived macrophages in human diseases where nerve cells of the intestine are affected, for instance in obese and diabetic patients with abnormal gastrointestinal function. Moreover, the results can also be meaningful for brain research. In the brain, we have microglia, similar long-lived macrophages that play an important role in neurological conditions such as Alzheimer’s and Parkinson’s disease. Scientists currently believe that nerve cells in these patients die off because microglia do not provide sufficient care. Maybe one day, research of the intestine can offer us a better understanding of these brain conditions,”

concludes Boeckxstaens.

Identifying the various subtypes of tissue-resident macrophages, and understanding how these cells meet the functional needs of their tissue microenvironment is one of the major challenges facing the field of immunology. Future research is needed to investigate the presence of these macrophages in animals and humans.

Sebastiaan De Schepper, Simon Verheijden, Javier Aguilera-Lizarraga, Maria Francesca Viola, Werend Boesmans, Nathalie Stakenborg, Iryna Voytyuk, Inga Smidt, Bram Boeckx, Isabelle Dierckx de Casterlé, Veerle Baekelandt, Erika Dominguez Gonzalez, Matthias Mack, Inge Depoortere, Bart De Strooper, Ben Sprangers, Uwe Himmelreich, Stefaan Soenen, Martin Guilliams, Pieter Vanden Berghe, Elizabeth Jones, Diether Lambrechts, Guy Boeckxstaens
Self-Maintaining Gut Macrophages Are Essential for Intestinal Homeostasis
Cell; August 30, 2018DOI:https://doi.org/10.1016/j.cell.2018.07.048

Image: long-lived macrophages in the intestines of mice (in green) make contact with the nerve cells of the gastrointestinal tract (in red). The macrophages provide growth factors for the nerve cells. The nerve cells die off without the macrophages. Credit: © TARGID – KU Leuven

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