Subterranean Fishes of the World

4308

2019

AIM 2019

59

Host-parasite interactions are one of the major driving forces in evolution. The recent epidemiological transitions in modern human societies, however, drastically decreased parasite diversity in developed countries. While these epidemiological transitions led to an increased life expectancy, the decreased parasite diversity is hypothesized to be a main cause for the increase of autoimmune diseases in human populations of developed countries. This indicates that the interactions between host and parasite not only created a co-evolutionary dynamic, but also represent a necessity for a vertebrate host to develop a functional immune phenotype. So far, this “Old Friends” hypothesis is largely based on descriptive data from humans but underlying causes for the maladaptive host immune response (i.e. development of autoimmune disorders) are unknown. To understand how environmental changes such as the loss of parasite diversity influence the evolutionary trajectory of the vertebrate host immune system, we use the emerging animal model Astyanax mexicanus. Since surface and cave morphotypes of A. mexicanus adapted to different habitats with extreme differences in overall biodiversity, we hypothesized that the environmental change during cave colonization caused distinct changes in the immune response of cave fish. Indeed, as in human populations of developed countries, we found an increased inflammatory response of cave fish towards bacterial endotoxins in-vitro and in-vivo. Contrary to this phenotype, cellular immune responses, such as phagocytosis, are drastically decreased in cave fish. Using a novel image-based immune cell phenotyping approach and single-cell RNA sequencing, we identified a shift in the overall immune cell composition of the main hematopoietic organ in cave fish. This shift mainly results in an overall decrease of immune cells that mediate inflammation and cellular immune responses such as phagocytosis (i.e. neutrophils and monocytes). This suggests that the increased inflammatory response of cave fish is compensated by a reduction of the immune cells that mediate this response. Furthermore, we found that immunopathological phenotypes in visceral adipose tissue are drastically reduced in cave fish, suggesting that the changes in the immune cell composition enable an increased fat storage in cave fish without the immunopathological consequences as described for other vertebrate hosts. Future investigation in this direction will not only provide important insights into the immune system of the emerging model organism A. mexicanus in general but will also help to elucidate the evolutionary trajectory of vertebrate hosts in an environment with low parasite diversity.

1

Astyanax Interrnational Meeting