Annäherung an "Alte Freunde" mit einem neuen Modell: Wie Parasitenvielfalt die Anpassung von Astyanax mexicanus an die Höhle beeinflusste
Zusammenfassung der Projektergebnisse
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". This species consists of two distinct morphotypes; an ancestral river morphotype (surface fish) and the derived cave morphotypes (cavefish) that colonized different cave environments approximately 50,000 - 200,000 years (50,000 - 200,000 generations) ago. The cave morphotypes differ in a variety of morphological, physiological and behavioral phenotypes from the ancestral river population. Importantly, one aspect of the cave environment is the overall decrease in biodiversity and parasite diversity. Given the fact that the cavefish and surface fish are interfertile and can be bred and raised in the lab makes A. mexicanus a well-suited animal model to study how the loss of parasite diversity affects the phenotype and genotype of the vertebrate immune system. Here, we show that the cave environment has a lower parasite abundance than the river habitat, which is resembled by lower parasitic infection rate and lower immune activation of wild caught cavefish compared to wild-caught surface fish. This ecological difference between cave and river habitat resulted also in the reduction of MHC-II allele diversity in cavefish suggesting that genomic adaptational changes occurred. On a physiological level, cavefish display a more sensitive proinflammatory immune response towards bacterial endotoxins. Surprisingly, cellular immune responses, such as phagocytosis, are drastically decreased in cavefish. 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. While surface fish invest evenly into the innate and adaptive immune system, cavefish shifted immune investment to the adaptive immune system, and here, mainly towards specific T-cell populations that promote homeostasis during inflammation. Additionally, inflammatory responses and immunopathological phenotypes in visceral adipose tissue are drastically reduced in cavefish. Our data indicate that long term adaptation to low parasite diversity coincides with a more sensitive immune system in cavefish, which is accompanied by a reduction of the immune cells that play a role in mediating the pro-inflammatory response. This work is the basis for future projects that will aim at identifying the genetic basis of different immune investment strategies and immune sensitivity to uncover potential genetic factors that contribute to the development of autoimmune diseases.
Projektbezogene Publikationen (Auswahl)
- (2020) Adaptation to low parasite abundance affects immune investment and immunopathological responses of cavefish. Nature ecology & evolution 4 (10) 1416–1430
Peuß, Robert; Box, Andrew C.; Chen, Shiyuan; Wang, Yongfu; Tsuchiya, Dai; Persons, Jenna L.; Kenzior, Alexander; Maldonado, Ernesto; Krishnan, Jaya; Scharsack, Jörn P.; Slaughter, Brian D.; Rohner, Nicolas
(Siehe online unter https://doi.org/10.1038/s41559-020-1234-2) - (2021) Image3C, a multimodal image-based and label-independent integrative method for single-cell analysis. eLife 10
Accorsi, Alice; Box, Andrew C.; Peuß, Robert; Wood, Christopher; Sánchez Alvarado, Alejandro; Rohner, Nicolas
(Siehe online unter https://doi.org/10.7554/eLife.65372) - (2018). Early adipogenesis contributes to excess fat accumulation in cave populations of Astyanax mexicanus. Dev. Biol., 441(2), 297-304
Xiong, S., Krishnan, J., Peuß, R., & Rohner, N.
(Siehe online unter https://doi.org/10.1016/j.ydbio.2018.06.003)
