Immune System Response Directed by ‘Gut Reaction’ to Illness

SIGNAL projection from cells in the infected guts of mice influences the programming of immune system cells to either repair or protect the body, according to new research.

When the body is infected or injured, monocyte cells are quickly summoned to the exact area where act according to the scenario, either protecting the body from aggressive infection or assisting wound healing. In a bid to identify more about how and why the monocyte cells are programmed as they are, researchers examined how monocytes in mice responded to toxoplasmosis, a parasitic infection of the gut. They discovered that immediately after the infection had entered the gut, the tissue started to communicate with other regions of the body in order to affect the immune system.

Dr John Grainger, co-principal investigator, Faculty of Life Sciences, The University of Manchester, Manchester, UK, explained: “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-programme monocytes with the appropriate function to either protect or repair.” This signalling meant that monocytes already knew how to operate prior to reaching 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,” said Dr Grainger. “Your initial gut feeling about the infection is literally telling the rest of the system what to do.”

Dr Grainger speculated that it may be feasible to develop drugs that target the monocyte programming mechanisms in the bone marrow, although such a strategy is currently restricted by a lack of knowledge regarding bone marrow. The study also revealed that the signals can reprogramme the monocytes to repair upon encountering 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,” said Dr Grainger, who added that further tests are required to ascertain whether certain species of commensal bacteria are responsible for affecting monocyte function.

The team is collaborating with other research groups to continue their study of monocytes. In particular, they are attempting to recognise circumstances where this type of signalling may have failed, such as in inflammatory bowel diseases.

(Image: freeimages.com/aneczka-ja)

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