Immune cell discovery explains inappropriate inflammatory responses

Scientists have discovered how the immune cells trigger an inflammatory response - a finding that may pave the way for new treatments for many human diseases. Immune cells play essential roles in the maintenance and repair of our bodies. When we injure ourselves, immune cells mount a rapid inflammatory response to protect us against infection and help heal the damaged tissue.

“While this immune response is beneficial for human health, many human diseases (including atheroscelerosis, cancer and arthritis) are caused or aggravated by an overzealous immune response,” said Helen Weavers, from the University of Bristol in the UK.

“A greater understanding of what activates the immune response is therefore crucial for the design of novel therapies to treat these inflammatory disorders,” Weavers said.

“Our study found that immune cells must first become ‘activated’ by eating a dying neighbouring cell before they are able to respond to wounds or infection,” she said. “In this way, immune cells build a molecular memory of this meal, which shapes their inflammatory behaviour,” she said.

The researchers used the fruit fly (Drosophila melanogaster) to study how a particular immune cell (the macrophage) becomes activated in order to respond to injury or infection.

Using the fly researchers were able to make time-lapse movies of the dynamic behaviour of the immune cells as they migrate within a living organism. It also allowed them to easily manipulate different genes and signalling pathways within the fly, to test which genes are important for immune cell behaviour.

Using genetics, the researchers dissected the mechanism by  which the molecular memory is generated within the immune cell. Ingestion of the dying cell activates signalling via a calcium flash, which leads to an increase in the amount of an important damage receptor Draper in the immune cell.

High levels of this receptor enable the ‘primed’ immune cell to sense the damage signals that entice them towards a wound during inflammation. Without this priming, the cells are blind to wounds and infections.

“Our work has important implications for human health, given that the pathology of many human diseases is often caused by an inappropriate inflammatory response,” said Paul Martin from University of Bristol.

“Understanding how one signal (in this case a dying cell) can influence the ability of an immune cell to respond to a subsequent signal is a major step towards finding novel ways to clinically manipulate immune cells away from sites of the body where they are causing the most damage,” Martin said. The study was published in the journal Cell.