Iron drives fungal infection in lung transplants, says study

When scientists transplanted the windpipes of mice, they found that iron accumulated in the grafted tissue. The high level of iron triggered the invasion of the fungus Aspergillus fumigatus​, found the research team led by the Stanford University School of Medicine.

The researchers found the same pattern of iron distribution when they looked at biopsies in human lung transplant patients. Levels of iron were higher in the transplanted tissue than in the host.

In cellular experiments that made iron more available to the mould, invasion of Aspergillus ​occurred. The extent of invasion was also linked to the amount of free iron present.

The results suggest that increased iron is a major determinant of Aspergillus​ colonisation. The findings may help explain why some lung transplant patients become infected, but not others, depending on their iron levels. .  

"You could have lots of Aspergillus in the airway, which is fine because it’s everywhere, but it wouldn't penetrate the tissue unless there was iron beneath it,"​ commented senior author Professor Mark Nicolls.

"Iron is like fertilizer for the Aspergillus,” ​he added.

Significance​

The Aspergillus ​mould is extremely common, even in hospitals with highest standards of hygiene. "It's everywhere -- we inhale thousands of these spores per day,"​ said Professor Joe Hsu, MD, lead author of the study.

Aspergillus​-related conditions occur in one-third of lung transplant patients, explained the scientists. These include severe asthma and lower respiratory tract infections. The most common cause of death in such cases is organ rejection, during which accelerated fungal invasion develops.

The scientists reduced the extent of Aspergillus ​invasion in the mice by injecting a chemical that reduced the availability of iron.  The scientists believe that lowering iron levels may change the behaviour of the fungus so that it does not aggressively colonise lung tissue.

The next step would be to test the effectiveness of such an approach in humans, said Professor Hsu. As high iron levels are also present in other lung diseases, he suggests that such a technique may have wider applications across the field of pulmonary care.

Source:  Science Translational Medicine​
Volume 10, Issue 429, eaag2616    DOI: 10.1126/scitranslmed.aag2616​​
“Microhemorrhage-associated tissue iron enhances the risk for Aspergillus fumigatus invasion in a mouse model of airway transplantation”​
Authors: Joe L. Hsu, Mark R. Nicholls et al​