The life cycle of a microscopic worm is offering scientists new insights into a deadly fungal disease, which affects around 1 in 10 patients with HIV.
Scientists at the University of Birmingham are using nematode worms to examine the development of the Cryptococcus fungus. Cryptococcus can cause severe infections in patients with weakened immune systems and is therefore a particular health problem for AIDS patients. Understanding the effects of the fungus in the nematode will help researchers to understand how the infection develops in humans.
The research, which is published online in Genetics, showed that resistance to the fungus was linked to the natural lifespan of the worm. So worms with a longer natural lifespan survived infection with Cryptococcus for longer.
Dr Robin May who led the research said: "The link between resistance and life-span was extremely pronounced, so worms with a long lifespan, like the New York strain (C. remanei, EM464), survived the fungus for longer. This suggests that animals with a longer lifespan invest more in their immune response to ensure they survive long enough to reproduce. It is also interesting because it shows that similar organisms show a markedly different immune response to the fungus."
The researchers found a similar pattern when looking at the difference between the sexes of nematode species exposed to Cryptococcus. In one of the most commonly studied species (C. elegans) males live up to 20% longer than hermaphrodite worms. The Birmingham team showed that males also showed far stronger resistance to Cryptococcus than hermaphrodites.
Because of the unique biology of the nematode, the Birmingham team were able to show that this immune response could be switched on and off by changing pathways that determine the worm’s sex.
Dr May continues: "Cryptococcus is a fascinating organism. Although it is a relatively common yeast-like fungus, we still don’t understand why only a few species are pathogenic to humans. By looking at the progress of the fungus in the nematode, we are able to better understand the biological processes at work. Our study showed that immunity to the fungus was very variable and linked, in ways that we do not yet understand, to the natural ageing process.
We are now taking this work on to look at how human defence cells (macrophages) respond to the fungus to develop an understanding of how the fungus operates in humans. Hopefully by understanding the basic biology of Cryptococcus, we can eventually find ways to reduce people's risk of infection."