Dr Margarida Castro Gomes Spencer

Bacterial infections are the second leading cause of mortality worldwide. Most causative bacterial agents, including Staphylococcus aureus and Pseudomonas aeruginosa, have developed antimicrobial resistance (AMR), thereby hampering effective treatment with antibiotics. There is an urgent need for innovative strategies to tackle the current AMR crisis, which is projected to cause 10 million deaths by 2050. Trained immunity (TRIM), which involves reprogramming the innate immune system upon microbial exposure to enhance its response to infections, presents promising potential in combating AMR. Nevertheless, the full spectrum of microbial stimuli capable of inducing TRIM remains unidentified, leading to many unrecognised beneficial effects.

Commensal bacteria residing in the human gut are essential in enabling the immune system to recognise pathogens throughout the body. We investigate methods to utilise these bacteria in training innate immune cells, such as macrophages and neutrophils, to improve infection control. We use the zebrafish model to study complex host-pathogen interactions and test whether different microbial stimuli can induce TRIM. Zebrafish are a uniquely advantageous model because only innate immune responses are present during early development, and their optical transparency facilitates in vivo, non-invasive, real-time imaging of host cells interacting with bacteria.

This emerging understanding of immune function has the potential to inform the development of therapeutic strategies that enhance innate immune responses against infections caused by antimicrobial-resistant pathogens.