Natalie Parletta
Natalie Parletta is a freelance science writer based in Adelaide and an adjunct senior research fellow with the University of South Australia.
Australian researchers have found new insights into how the immune system responds to malaria infection, which they say could help understand and treat it, as well as other conditions such as hepatitis, HIV and lupus.
In a laboratory mouse model, they discovered that malaria infection causes strong inflammatory signals that trigger the immune system to make potent antibodies to fight the disease.
These signals are also seen in human malaria infections as well as chronic viral infections and autoimmune diseases, and may lead to improved therapies, says Diana Hansen from the Walter and Eliza Hall Institute, who led the research.
Half the world’s population lives at risk from the mosquito-borne infection, which afflicts more than 200 million people each year – more than half being children under five – and is fatal in nearly a quarter of these cases.
Efforts to control and treat the disease, most concentrated in sub-Saharan Africa and India, include insecticide-treated homes and mosquito nets, artemisinin-based combination therapy, vector control, seasonal chemoprevention and biocontrol.
Although some progress has been made, declines in the disease have stalled, with concerns that targets to reduce its incidence and mortality rates by at least 40% by 2020 will not be achieved.
Hansen’s team has spent the last decade focussing on the host’s poor immune response to malaria, which until now was largely attributed to the parasite’s ability to evade detection by the immune system.
People must be continually exposed to malaria over many years to develop immunity, explains Hansen, during which time they are sick and can spread the disease.
“We wanted to know what makes malaria infection different to so many other diseases, where a single exposure confers immunity for life.”
Previously, they found that inflammatory signals activated molecules that blocked immune T cells, hampering their ability to instruct B cells to make antibodies that fight disease.
“When we began this study,” she says, “we expected to see that inflammation was also having a negative effect on B cells.
“In fact, we found the opposite was true. The inflammatory signals were improving the quality of the antibodies produced, by sending B cells to an elite training ground, where they underwent an exhaustive program to become ‘professional disease fighters’.”
These potent antibodies were previously undetected, and it begs the question, why do people respond so poorly to malaria infection?
It seems that while the inflammatory signals improve the quality of the antibody response, they limit its scope, Hanson explains.
“So the B cells, even though they are of elite quality, are not able to have as much impact on future infections.”
This potent antibody response is what other chronic viral infections such as HIV and hepatitis C need, so the team hopes the “molecular switch” they’ve identified will offer a more precise target for treating those diseases as well.
Conversely, B cells that are primed to make antibodies can also attack the body’s own tissues, leading to autoimmune diseases such as lupus, so turning the switch off might prevent those same molecules from producing self-destructive antibodies.
The research is published in the journal Cell Reports.
