Associate Professor Anthony Jaworowski and researcher Jingling Zhou
Burnet Institute researchers have identified the type of monocyte - white blood cells critical to immune function - best equipped to attack the malaria parasite, along with new insights into how the monocyte carries out this task.
Associate Professor Anthony Jaworowski describes the findings as exciting and potentially important for the development of malaria vaccines.
The paper, published in the journal BMC Medicine, shows the ‘intermediate’ subset of monocytes ingest red blood cells infected with the malaria parasite, which is important for the control of malaria in the blood and for orchestrating subsequent immune responses.
“Most research in this field uses purified white blood cells which are presented with infected red blood cells to see what happens, but we looked at the monocytes using small samples of whole blood,” said Associate Professor Jaworowski.
“That’s technically more difficult, but of course it resembles the situation in the body far more accurately than using purified cells.
“Researcher Jingling Zhou noticed that when you do the experiment using whole blood containing antibodies recognising the infected red blood cell there’s only one type of monocyte that ingests the infected red blood cells, and that’s the intermediate population of monocytes.
“This work shows that they are their own unique population with special properties. They are the only monocytes that can efficiently digest parasitised red blood cells.”
Associate Professor Jaworowski said Ms Zhou was also able to identify the process enabling intermediate monocytes to ingest infected red blood cells.
“What Jingling has shown is that the intermediates express a receptor on their surface called CD16 which recognises the antibodies attached to the red blood cell and that is absolutely required for this ingestion,” Associate Professor Jaworowski said.
“But surprisingly, what Jingling also found was that CD16 though essential, was not sufficient to cause ingestion.
“The ingestion needed the participation of another type of receptor called the complement receptor. In combination, the complement receptor and CD16 are both required to get this efficient internalisation.”
Associate Professor Jaworowski said the research highlights the importance of the complement receptor in vaccine development and offers two clear paths for further investigation.
The first is to look further into what the intermediate monocyte does after it ingests the parasite and how is it orchestrating other arms of the immune system to combat infection.
“That’s not known and that’s an area that we’re actively pursuing,” Associate Professor Jaworowski said.
“But we can also take these findings into looking at vaccine candidates and see, if we measure the ability of the vaccine to both promote the correct antibody response in terms of ingestion and also complement activation, whether that better predicts protection.
“That’s the ultimate goal, to develop an assay that will predict the ability of a vaccine to protect people who get vaccinated.”
Professor Jaworowski said it was important for funding bodies to continue to support research at the interface between basic laboratory research and clinical work.
“We’ve been lucky enough to have continued NHMRC support for this project,” he said. “We’re very excited by the research. I think it’s a great outcome.”