Researchers have discovered that immune system cells in mice are programmed in advance to either repair or protect the body after receiving signals from cells in the infected gut.

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Monocytes can be programmed to either fight infections or repair damaged tissue.

Prior to the study – published in Immunity – experts believed that immune cell programming only occurred once the cells had arrived at the point of injury or infection.

“We were really surprised by this finding as it went against what we had predicted,” says researcher Dr. John Grainger, of the University of Manchester, UK. “Therapeutically this changes how we want to try to reprogram these cells.”

Specialized cells called monocytes are produced in the bone marrow and circulated around the body in the bloodstream. When the body is injured or infected, monocytes are swiftly called to the precise area where they act according to the situation, either protecting the body from aggressive infection or aiding wound healing.

Sometimes monocytes can be programmed incorrectly and, rather than defending the body, can cause inflammation that leads to severe conditions such as bowel disease or cancer.

So far, scientists have been unable to identify how and why the monocytes are programmed as they are. To investigate, researchers led by Dr. Grainger and Dr. Yasmine Belkaid, from the National Institute of Allergy and Infectious Diseases (NIAID), examined how monocytes in mice responded to a parasitic infection.

Toxoplasmosis is caused by the parasite Toxoplasma gondii and can infect the gut through the consumption of undercooked meat. The parasite is also known to be present in the feces of cats.

The researchers discovered that as soon as the infection invaded the gut, the tissue began to communicate with other parts of the body in order to alter the immune system. Dr. Grainger explains:

One particular cell-type in the gut, the dendritic cell, can act as a beacon sending out long-range signals to the bone marrow where monocytes are produced. Cells in the bone marrow then pick up the signal and pre-program monocytes with the appropriate function to either protect or repair.”

This signaling meant that the monocytes already knew how to function before they had even reached the affected tissue.

“This turns on its head the idea that monocytes are programmed when they get to the infected gut and puts the early signals coming out from the gut at the centre of monocyte programming,” says Dr. Grainger. “Your initial gut feeling about the infection is literally telling the rest of the system what to do.”

Dr. Grainger speculates it may be possible to develop drugs that target the monocyte programming mechanisms in the bone marrow, though, at present, not enough is known about the bone marrow for this to be done.

Another aspect of the newly-discovered signaling mechanism revealed by the study was that the signals can also reprogram the monocytes to repair when they encounter good bacteria (commensal bacteria) in the gut.

“We were really blown away by the fact that the monocytes could change their function depending on the commensal bacteria in the gut,” says Dr. Grainger, adding that they now need to test whether particular species of commensal bacteria are responsible for influencing monocyte function.

The team is working with other research groups to continue their investigations into monocytes. In particular, they are attempting to identify situations where this form of signaling may have gone wrong, such as in inflammatory bowel diseases.

Toxoplasma gondii has also featured in other recent studies. Earlier this week, Medical News Today reported on a study that linked cat ownership in childhood with mental illness in later life due to the risk of exposure to the parasite.