The Human Pathogen and the Fish Pathogen Trigger a Core Set of Late Innate Immune Response Genes in Zebrafish Larvae.

Zebrafish is a natural host of various species and a surrogate model organism for tuberculosis research. is evolutionarily one of the closest non-tuberculous species related to and shares the majority of virulence genes. Although zebrafish is not a natural host of the human pathogen, we have previously demonstrated successful robotic infection of zebrafish embryos with and performed drug treatment of the infected larvae. In the present study, we examined for how long can be propagated in zebrafish larvae and tested a time series of infected larvae to study the transcriptional response via Illumina RNA deep sequencing (RNAseq). Bacterial aggregates carrying fluorescently labeled could be detected up to 9 days post-infection. The infected larvae showed a clear and specific transcriptional immune response with a high similarity to the inflammatory response of zebrafish larvae infected with the surrogate species . We conclude that can be propagated in zebrafish larvae for at least one week after infection and provide further evidence that is a good surrogate model for . The generated extensive transcriptome data sets will be of great use to add translational value to zebrafish as a model for infection of tuberculosis using the infection system. In addition, we identify new marker genes such as and CD180 that are induced by infection in zebrafish and in human macrophages at later stages of infection that can be further investigated.