Researchers have discovered how part of the body's immune system could better combat a leading cause of death for people with cystic fibrosis (CF).
A team led by The University of Queensland's Professor Peter Sly and Dr Abdullah Tarique has identified how macrophages - the white blood cells that fight infection in the body - function differently in people with CF, compared to others.
"Macrophages play a critical role in fighting infection, especially in the lungs," Professor Sly said.
"They're the 'Pac-Man' cells that find and 'gobble up' bacteria and pathogens such as mycobacterium abscessus (MABS).
"We found people with CF have multiple defects in their macrophages that leave them more vulnerable to infection, even when taking the most effective CF drug treatment available."
Professor Sly said MABS posed the biggest infection risk for people with CF.
"MABS is resistant to many antibiotics which makes treatment complex and often unsuccessful," he said.
"The infection can exclude a patient from being eligible for a lung transplant and is a leading cause of death for people with CF.
"And because of antibiotic resistance, MABS infections are increasing at alarming rates."
Professor Sly said in people with CF, macrophages aren't as efficient at both recognising and killing off bugs in the body.
"CF involves a defect in the CFTR protein, the channel on the cell's surface responsible for transporting ions and chlorine in and out of cells," he said.
"That lack of chlorine transport means macrophages don't activate their killing functions to 'eat' the bugs.
"A second important mechanism in macrophages is also deficient - the zinc transport of proteins.
"Zinc is a potent antibacterial mechanism used to poison bacteria, but with less zinc and less zinc transporter proteins in CF macrophages, they're less able to fight the infection."
Professor Sly said a third defect - in the mitochondria - is perhaps the most significant.
"Mitochondria are the batteries or power packs of cells, and produce things called reactive oxygen species to kill bacteria.
"In CF, not only are macrophages less able to make these reactive oxygen species, but they're also not able to keep reproducing them to increase their mitochondrial mass when infected."
The research also examined treatments for CF and found even the most effective drug doesn't boost macrophage's ability to kill MABS.
"Elexacaftor-tezacaftor-ivacaftor (ETI) has been revolutionary in CF treatment by improving lung function in many people, meaning fewer exacerbations and hospitalisations," Professor Sly said.
"But it doesn't fix this part of the immune system, which is why people with CF still get these infections.
"Our findings show we now need to accelerate research into different mechanisms of increasing macrophage function, to identify and initiate killing strategies for MABS.
"This could significantly reduce the impact of these infections for people with CF."
Read the research in Proceedings of the National Academy of Sciences.
Collaboration and acknowledgements
The research team included scientists from UQ's Child Health Research Centre , Professor Matt Sweet 's group at UQ's Institute for Molecular Bioscience, the Queensland Children's Hospital, Infectiologie et Santé Publique, Université de Montpellier, Institut de Recherche en Infectiologie de Montpellier, Gold Coast University Hospital and Griffith University.
