SHIELDing life: enhancing trained immunity against fungal threats
( SHIELD )

Interventions

Therapeutics

Research Project: 2025-04-01 - 2028-03-31
Total sum awarded: €1 219 850

Fungal infections significantly impact global health, particularly affecting immunocompromised individuals like chemotherapy patients, leading to approximately 1.5 million deaths annually. The rise of drug-resistant fungi, such as C. auris and A. fumigatus, highlights the need for innovative treatments beyond current antifungal therapies. This project explores trained immunity (TI) potential to enhance host defense against fungal infections, offering a solution to combat antimicrobial resistance. TI is a newly introduced mechanism that refers to an enhanced state of innate immune cells following exposure to specific agents.Objectives include:1. Identifying compounds that induce TI against fungal infections in vitro.2. Assessing these compounds' efficacy against fungal infections ex vivo in chemotherapy patients' blood samples.3. Investigating the molecular mechanisms of TI induction through multi-omics analysis.4. Characterize the functional mechanisms of TI against fungal infection in immunocompromised animal models.In recent years, TI has demonstrated a great protentional to become a gamechanger approach against infectious diseases. Here, we aim to investigate whether TI can improve the immune system's capability to counteract fungal pathogens, even those resistant to drugs. Successful outcomes are likely to transform fungal infection treatment, especially for those at high risk of severe infections. This project’s ultimate goal is to significantly reduce fungal infections' global burden and introduce innovative infectious disease management strategies.

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  • Andres Jorge Dominguez, Stichting Radboud Universitair Medisch Centrum, Netherlands (Coordinator)
  • Yahya Sohrabi, University Hospital Münster, Westfälische Wilhelms-Universität, Münster, Germany (Partner)
  • Boris Novakovic, Murdoch Children’s Research Institute, Australia (Partner)
  • Eva Kaufmann, Queen’s University, Canada (Partner)

Fungal infections are a major health problem worldwide, hitting hardest those with weakened immune systems, such as cancer patients undergoing chemotherapy. Every year, these infections are responsible for over a million deaths globally. A growing concern is that many fungi are becoming resistant to existing drugs, making infections harder to treat.Our research explores an exciting concept known as "trained immunity". This approach aims to boost the body's natural defenses, enabling it to fight off fungal infections more effectively, including those resistant to current treatments. Imagine giving your immune system a training program that makes it stronger and more prepared to defend against these dangerous fungi.The goal of our project is to unlock new ways to prevent and treat fungal infections. By harnessing the power of trained immunity, we hope to provide a beacon of hope for those at high risk of these infections, particularly individuals undergoing chemotherapy. This research has the potential to revolutionize how we combat fungal diseases, offering new strategies to protect vulnerable populations and tackle the challenge of drug-resistant fungi.

Call

2024 - Interventions moving forward to promote action to counteract the emergence and spread of bacterial and fungal resistance and to improve treatments