Disruption of Trim9 function abrogates macrophage motility in vivo

ABSTRACT: The vertebrate immune response is comprised of multiple molecular and cellular components that interface to provide an adequate defense against pathogens. Although much is known on how individual molecules or cells respond to infection, an understanding of the whole-organism response to pathogen exposure remains unresolved, due to the dynamic complexity of the immune system and its interdependent innate and adaptive functionality. Zebrafish larvae provide a unique model for overcoming this obstacle as larvae can successfully defends themselves from pathogens while lacking a functional adaptive immune system during the first few weeks of life, making it possible to examine exclusively the innate immune response in a whole-organism context. It was hypothesized that the transcriptional response of zebrafish larvae to immune agonists would identify known immune-response genes as well as reveal genes that mediate innate immunity in novel ways. In order to test this hypothesis, zebrafish larvae were exposure to the chemically diverse immune agonists, polyinosine-polycytidylic acid (PolyIC) and synthetic triacylated lipoprotein (Pam3CSK4) and transcriptome analyses completed using microarray analyses. This strategy successfully identified known immune response genes, as well as genes that had not been implicated in immune function, including the E3 ubiquitin ligase, tripartite motif 9 (trim9). Although Trim9 expression has been described as “brain specific”, here we demonstrate elevated levels of trim9 transcripts in macrophages after immune stimulation. As Trim9 has been implicated in axonal migration, we investigated and demonstrate that disruption of Trim9 function impairs macrophage chemotaxis and cellular architecture in vivo. These results demonstrate that Trim9 mediates cellular movement and migration in macrophages as well as neurons.

ORGANISM(S): Danio rerio

PROVIDER: GSE81317 | GEO | 2017/09/26

SECONDARY ACCESSION(S): PRJNA321265

REPOSITORIES: GEO