A study of how the brain immune system responds to powerful forces of cave adaptation in the Mexican tetra 3982

Abstract Description The Mexican tetra A. mexicanus, with its phenotypically distinct cave- and surface-dwelling conspecific morphs, has provided broad insight into adaptive phenotypes. Recent research highlights the intricate interplay between the brain and immune system, leading us to hypothesize that the unique environmental pressures of cave life have reshaped intercellular communication within the immune system of the brain. To investigate this, we generated single-nuclei and spatial transcriptome atlases of the adult brains of surface and cavefish to explore immune system adaptation. Analysis of 116,000 nuclei allowed us to annotate 35 cell types, including of immune cell clusters showing mixed lineage characteristics. Subsequent reclustering of immune cells identified 19 transcriptionally distinct populations with multiple classifications of microglia (n = 4), macrophages (n = 2), and T cells (n = 3) seen. The evaluation of cell type compositional shifts using a Bayesian proportionality test, showed significant change for a population of microglia and T cells, in both higher numbers observed in the cave adapted fish. Interestingly, preliminary evaluations of other A. mexicanus organ-systems also show immune cell type specific compositional differences. This catalog of immune cell changes in the genetically adapted brain enhances our understanding of how gene regulatory networks mediate the integration of immune and nervous system functions. Funding Sources NIH R24OD030214 Topic Categories Veterinary and Comparative Immunology (VET)