An Irish-led study has shed new light on how the immune system deals with a parasitic worm infection that affects millions of people every year.

The study focused on the parasitic filarial nematode worm which infects the pleural cavity - the space between the lungs and the chest wall. Despite its clinical relevance, little research into the immunology of the pleural cavity has been carried out.

According to the World Health Organization, 863 million people are at risk of developing filariasis, a painful and potentially disfiguring disease caused by the worm.

While prevention efforts and medical interventions have been successful in reducing the number of human infections, over 70 million people are estimated to be infected each year.

This latest study was undertaken by researchers from Trinity College Dublin (TCD) and the University of Manchester in the UK. They have shown how a specific type of T cell, which is a type of white blood cell, activated by the worms, signals to other immune cells called macrophages to transform and expand in a manner which eliminates the infection by a filarial nematode.

They noted that many people appear to be able to control filarial worm infection, however others harbour hundreds of worms, some of which go on to develop tissue damage caused by an inappropriate immune reaction to worms.

This study is relevant because scientists do not fully understand why some people can handle infection well while others suffer from severe pathology.

Compared with worms that live in the gut, there is less understanding of how the immune system controls infection with filarial nematodes in body tissues.

“The signalling molecules or cytokines called IL-4 and IL-13 have long been known to activate macrophages, but here we show that they do something surprising. They control the development of blood monocytes into tissue-resident macrophages at the worm infection site.

“These cytokines are transforming cells into a cell type suitable to fight the worm. What’s more, if we prevent this transformation from occurring then the immune system can no longer kill these worms,” explained the study’s lead author, Dr Conor Finlay, of TCD’s School of Medicine.

The researchers also showed how T cells, which can generate memory of prior infection, control this whole process by producing the cytokines on macrophages that then go on to kill the worms.

According to the study’s supervisor, Prof Judi Allen of the University of Manchester, her group has been trying to understand what role macrophages play during infection of worms that live in the tissues “for many years”.

“The finding that they contribute to worm killing is exciting for me personally and opens up even more questions. Tissue-resident macrophages have important roles in controlling inflammation and repairing damaged tissue, so our model of how T cells and cytokines control their development has wide applications in other diseases,” she pointed out.

This was emphasised by Dr Finlay who insisted that this study “is not just about worms”.

“We have characterised the immune system of the pleural space to the highest level of detail yet known. Being so close to the lungs, the pleural cavity is a site of enormous clinical relevance in congestive heart failure, pneumonia, cancer and fibrotic diseases. Despite this we know relatively little about the immune response in the pleural space,” he said.

He added that despite this major step forward, many questions remain unanswered.

“We have shown that these macrophages are required for worm killing, now we need to show exactly how they do that. This study leads us to believe that genes which control macrophage function may hold the key to explain the genetic predisposition to infection with parasitic worms.”

The study is published in the journal, Immunity, and can be viewed here.