Decoding Immune Evasion by Worm Parasites
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.
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Subscribe for FREEThe study shows that heGDH acts as a molecular switch in macrophages, critical innate immune cells. Once internalized 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 analyzing and modifying the protein’s structure, researchers pinpointed features essential to its unique activity, distinguishing it from its mammalian counterpart.
Implications for Vaccines and Therapeutics
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 optimized 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. Julia Esser-von Bieren adds: “Our findings could lead to transformative treatments for infectious diseases and inflammatory conditions like asthma.”
Towards a Future of Broad-Acting Biotherapeutics
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% 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.
Reference: Bohnacker S, Henkel FDR, Hartung F, et al. A helminth enzyme subverts macrophage-mediated immunity by epigenetic targeting of prostaglandin synthesis. Sci. Immunol. 2024. doi: 10.1126/sciimmunol.adl1467
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