Autophagy shapes Debaryomyces hansenii invasion in Crohn’s disease

While pathogenic fungi have been identified in the gut of Crohn’s disease (CD) patients, their role in triggering gut inflammation is unclear. We recently showed that a high proportion of CD patients have a unique fungal species, D. hansenii, in their inflamed gut mucosa. We used mouse models to identify that key immune cell types such as macrophages are responsible for the clearance of D. hansenii and subsequent healing of the gut wounds. However, whether host genetics affects the response to D. hansenii is unknown. We found that mice that are engineered to carry a CD susceptibility genetic mutation, termed ATG16L1 T300A, are less effective in clearing D. hansenii. We therefore propose to study how macrophages from CD patients and mice with the T300A mutation respond to D. hansenii infection. We will also examine if CD patients who carry the T300A mutation have higher fungal loads in their gut, and higher serum antibodies to D. hansenii. The results will allow us to identify a link between the most common CD-related genetic mutation and fungal infection.