Chemokine signaling in innate immunity of zebrafish embryos

Chemokines are signaling proteins that direct the migration and function of many cell types during development and responses of the immune system. The zebrafish embryo model is highly suited to investigate cell migration because of its optical transparency and availability of transgenic lines with fluorescently labeled cell types of the innate immune system. In this thesis, we analyzed the phylogenetic relationships between zebrafish and human chemokines and used Salmonella and Mycobacterium infection models to study the function of a zebrafish chemokine receptor gene, cxcr3.2, homologous to human CXCR3. Our data have demonstrated that cxcr3.2 is predominantly expressed in macrophages of the zebrafish embryo and plays an essential role in bacterial-induced macrophage migration and control of local infections. Furthermore, we used in vivo cell migration assays in wild type and cxcr3.2 mutant embryos to discover the putative ligand of the cxcr3.2 receptor. Injection of Cxcl11, an infection-inducible chemokine, resulted in the directional migration of macrophages in a cxcr3.2-dependent manner. As the first ligand-receptor pair with a proposed function in migration of zebrafish macrophages in response to bacterial infection, the identification of Cxcl11-Cxcr3.2 interaction is an important step towards understanding the chemokine signaling network underlying innate immune responses in the zebrafish model.