Researchers have uncovered a molecular strategy employed by worm parasites (helminths) to evade host immune defences – a discovery that opens new avenues for the development of innovative vaccines and therapies.
The study offers promising solutions for addressing major infectious diseases, allergies, and asthma by leveraging the unique immune-regulatory properties of helminths.
Helminths are known for their remarkable ability to regulate host immune responses, a trait that has intrigued scientists for its therapeutic potential.
However, the mechanism behind this phenomenon have remained elusive. In their study, the researchers could identify how a specific parasite protein, helminth glutamate dehydrogenase (heGDH), modulates host immunity to protect the parasite while limiting inflammation and tissue damage.
The study shows that heGDH acts as a molecular switch in macrophages, critical innate immune cells.
Once internalised by macrophages, the protein suppresses key functions necessary to trap and kill the parasite. Instead, it activates regulatory mechanisms that temper immune responses, preventing excessive inflammation.
Remarkably, heGDH achieves this through an epigenetic mechanism, suggesting lasting impacts on immune regulation. By analysing and modifying the protein’s structure, researchers pinpointed features essential to its unique activity, distinguishing it from its mammalian counterpart.
These insights open the door to new medical applications. Glutamate dehydrogenases (GDHs), which are found across many worm parasites, have emerged as promising targets for vaccine development.
At the same time, the research team is working on creating optimised variants of the protein that can evade detection by the human immune system.
“This study represents a major step toward leveraging the sophisticated immune evasion strategies of parasites for clinical benefit,” said Sina Bohnacker, the first author of the study.
Professor Julia Esser-von Bieren from the Center of Allergy and Environment (ZAUM) at Helmholtz Munich added: “Our findings could lead to transformative treatments for infectious diseases and inflammatory conditions like asthma.”
The discovery opens new avenues for addressing global health challenges.
Anti-parasite vaccines could mitigate the burden of helminth infections, which affect an estimated 24 per cent of the world’s population, according to the World Health Organization (WHO).
Meanwhile, therapeutic variants of heGDH could provide a novel approach to managing chronic inflammatory diseases, offering new hope for conditions like asthma, allergies, and other immune-related disorders.
