Grant: Travel Awards - Institute Community Support

The intestinal microbiota encompasses a community of commensal bacteria that live in a mutually beneficial relationship with their host. The profound importance of microbiota-host interactions in regulating the host immune system has been demonstrated in multiple illnesses, including cancer, diabetes and infectious diseases. Humanity has constantly faced the challenge of overcoming infectious diseases and, despite massive advancements in medicine, they continue to represent significant threats to health. Following infection with a pathogen, cells of the adaptive immune system display long-term changes in their function leading to the development of immunological memory. For a long time, immunological memory was considered an exclusive hallmark of the adaptive arm of the immune system. Yet emerging evidence has shown that innate immune cells can also adapt their function after previous insults and thereby also showing the ability to be 'trained'. However, unlike adaptive immune memory, innate memory is not pathogen-specific. For example, epidemiologic data suggests that some existing vaccines, such as Bacillus Calmette-Guérin (BCG), have beneficial effects against later infections unrelated to the target infectious agent. The underlying mechanisms involved in such innate memory are only beginning to be elucidated. The ability to successfully eliminate a pathogen has been associated with continuous crosstalk between the microbiota and the host immune system. However, whether the gut microbiota can induce such innate memory has not yet been studied. I propose to investigate the role of intestinal microbiota in the induction of innate memory and determine the impact on protective immunity. Understanding the mechanisms involved in 'training' innate cells will be critical for the design of new therapies and vaccines and allow us to better harness the power of the intestinal microbiota to boost immune responses to infections or modulate inflammation in chronic diseases.