Dr. Robert Peuß (IEB)

Dark World Rises: Establishing Cavefish as a model for human diseases

Dr. Robert Peuß

Many modern human diseases result from maladaptive responses to new environments. The recent reduction of parasite diversity in modern human populations for example is suspected to be a primary cause for the increase of autoimmune disorders. However, the long-term evolutionary consequences of decreased parasite diversity on the host immune system are not well understood. We used the cavefish Astyanax mexicanus to understand how loss of biodiversity, a hallmark of cave adaptation, influences the evolutionary trajectory of the vertebrate host immune system by comparing river with cave morphotypes. Using an image-based immune cell phenotyping approach and single-cell RNA sequencing, we identified a shift in the overall immune cell composition in cavefish as the underlying cellular mechanism associated with altered immune responses. The shift results in an overall decrease of immune cells mediating inflammation and cellular immune responses such as phagocytosis (i.e. neutrophils and monocytes). Moreover, we find that immunopathological phenotypes in visceral adipose tissue are drastically reduced in cavefish. Our data indicate that a more sensitive immune system in cavefish is compensated by a reduction of the immune cells that play a role in mediating the proinflammatory response. These findings reveal that cavefish are an effective model system to study the evolution of auto-inflammatory processes.