A team of scientists from the Faculty of Science at Charles University has achieved a major breakthrough in research into schistosomiasis, a serious tropical disease affecting more than 250 million people worldwide. Using advanced laser microdissection, the researchers have, for the first time, captured and analysed proteins secreted by the eggs of the human blood fluke Schistosoma mansoni directly within infected tissues of a living organism, rather than under artificial laboratory conditions.
Schistosomiasis is a dangerous parasitic disease caused by blood flukes of the genus Schistosoma. The main cause of health complications is the parasite's eggs, which become trapped in the host's liver or intestine. There, they secrete substances that trigger an inflammatory response and the formation of protective "barriers" known as granulomas, which are built around the eggs by immune cells. Long-term infection and the presence of eggs in tissues can have serious consequences, including enlargement of the liver and spleen, digestive problems, and increased blood pressure. Some species can even contribute to the development of cancer.
Although the eggs and the proteins they secrete play a key role in these processes, previous research has relied on artificially culturing the eggs and analysing them in vitro. This has distorted our understanding of which proteins the parasite actually releases into the host's body.
The team led by scientists from the Faculty of Science at Charles University overcame this problem using a technique known as laser microdissection. "Using this method, we excised precisely defined microscopic areas of tissue immediately surrounding the eggs in the liver and intestine of infected mice, without damaging the eggs themselves," said parasitologist Lucie Jedličková, who performed the microdissections using a specialised microscope.
Subsequent mass spectrometry analysis revealed a set of 149 parasite proteins that are consistently secreted into the surrounding tissue in both organs.
The research further showed that the overall protein profile of the eggs varies considerably depending on the organ in which they are located and the stage of infection. During the acute phase, eggs in the liver massively release key immune-suppressing molecules and tissue-degrading enzymes, whereas the composition of proteins released in the intestine remains much more stable over time. This difference reflects the fate of the eggs: those in the liver remain permanently trapped, while those in the intestine merely pass through the tissue on their way out of the host's body.
"Our results provide the first authentic insight into the parasite molecules that host tissues actually encounter. This is important, for example, for understanding how tissue damage develops and how immune responses arise in different affected organs. At the same time, our findings challenge the established 'textbook' assumption that eggs behave in the same way in all organs. They do not, and this has implications both for the interpretation of some earlier studies and, more importantly, for our practical understanding of the biology of schistosomes and the disease they cause," explains Tomáš Macháček of the Department of Parasitology at the Faculty of Science, Charles University, the study's lead author.
Why Is This Important, and What Makes the Research Groundbreaking?
Targeted development of drugs and vaccines:Precise identification of the proteins present at the parasite–host interface paves the way for a better understanding of how tissue damage develops and could also help identify new targets for vaccines or drugs against a parasite that affects 250 million people worldwide.
Moving beyond test-tube and textbook myths:The study corrects previously distorted ideas about the egg proteins secreted into host tissues—ideas that arose from studying eggs maintained for extended periods under unnatural in vitro conditions. It also highlights major differences between eggs found in different organs that have so far been largely overlooked.
Discovery of unconventional proteins:The mixture of secreted proteins—the schistosome's "molecular weapons"—has proved to be more diverse than previously thought. For example, the eggs also secrete proteins that were previously assumed to function exclusively inside cells.
