Programmable Innate Immunity

The innate immune system is traditionally viewed as a rapid but non-specific defence mechanism. However, growing evidence shows that innate immune cells can undergo durable functional reprogramming following exposure to microbial signals, therapeutics, or environmental stimuli. Our research explores whether innate immune responses can be deliberately programmed into defined functional states. These states may enhance host protection against infection, shape responses to therapeutics, or contribute to inflammatory disease.

We investigate the molecular mechanisms that control innate immune programming, including pattern recognition receptor signalling, inflammasome activation, and epigenetic regulation of immune responses. These processes are closely linked to phenomena such as trained immunity, where prior stimulation induces persistent changes in immune cell behaviour through metabolic and chromatin remodelling. Understanding these mechanisms may enable the development of therapeutic strategies that intentionally modulate innate immunity to improve disease prevention and treatment.

​

Key areas include:
Trained immunity and innate immune memory
Pattern recognition receptor signalling networks
Epigenetic regulation of innate immune responses
Immune programming by microbes, phages, and therapeutics
Engineering sustained innate immune protection

​

Operating across three interacting layers:
1. Immune sensing - Pattern recognition receptors detect therapeutic particles and microbial signals. These include TLRs, NLRs, and cytosolic DNA sensors that detect viral, bacterial, and nanoparticle stimuli.
2. Cellular reprogramming - Innate immune cells undergo metabolic and epigenetic changes that alter their future responsiveness. These changes include glycolytic rewiring, mitochondrial stress responses, and chromatin modifications associated with trained immunity.
3. Functional outcomes - The resulting immune state determines cytokine production, complement activation, inflammasome signalling, and therapeutic safety. This structure mirrors how trained immunity operates through metabolic and epigenetic reprogramming of innate cells.