Using Zebrafish to study Mucosal Immunity and Microbial Composition in the presence and absence of Adaptive Immunity

Study of the innate and adaptive immune pathways controlling bacterial colonization and mucosal cytokine responses has proven difficult in rodents, considering the extensive cross-talk between bacteria and innate and adaptive immunity. Zebrafish lack a functional adaptive immune system in the first weeks of life, enabling study of the interaction between the microbiota and the innate immune system in the absence of adaptive immunity. Also, several transgenic zebrafish exist that enable in vivo tracking of innate immune cells. Here, we show that in larval zebrafish, lacking adaptive immunity, Vibrionales species (known pathobionts) are able to grow out, coinciding with very low expression levels of chemokine Cxcl8. Using cell transfer experiments, we show that adoptive transfer of T lymphocytes into Rag1-deficient recipients suppresses outgrowth of Vibrionales species and enhances epithelial Cxcl8 expression in the zebrafish intestines, showing that zebrafish T lymphocytes play an important role in intestinal homeostasis. Furthermore, we will illustrate the advantage of using transgenic zebrafish to study innate cells in the intestinal mucosal compartment by showing our latest imaging data on the recruitment of macrophages and neutrophils in response to the enterocolitis-inducing chemical DSS.