Torraca, V., White, R., Sealy, I., Mazon-Moya, M., Duggan, G., Willis, A., Busch-Nentwich, E. and Mostowy, S. 2024. Transcriptional profiling of zebrafish identifies host factors controlling susceptibility to Shigella flexneri. Disease Models and Mechanisms. 17 (1) dmm050431. https://doi.org/10.1242/dmm.050431
| Title | Transcriptional profiling of zebrafish identifies host factors controlling susceptibility to Shigella flexneri |
|---|---|
| Type | Journal article |
| Authors | Torraca, V., White, R., Sealy, I., Mazon-Moya, M., Duggan, G., Willis, A., Busch-Nentwich, E. and Mostowy, S. |
| Abstract | Shigella flexneri is a human-adapted pathovar of Escherichia coli that can invade the intestinal epithelium, causing inflammation and bacillary dysentery. Although an important human pathogen, the host response to S. flexneri has not been fully described. Zebrafish larvae represent a valuable model to study human infections in vivo. Here we use a Shigella-zebrafish infection model to generate mRNA expression profiles of host response to Shigella infection at the whole animal level. Immune response-related processes dominate the signature of early Shigella infection (6 hours post-infection). Consistent with its clearance from the host, the signature of late Shigella infection (24 hours post-infection) is significantly changed, and only a small set of immune-related genes remain differentially expressed, including acod1 and gpr84. Using mutant lines generated by ENU, CRISPR mutagenesis and F0 Crispants, we show that acod1- and gpr84-deficient larvae are more susceptible to Shigella infection. Together, these results highlight the power of zebrafish to model infection by bacterial pathogens and reveal the mRNA expression of the early (acutely infected) and late (clearing) host response to Shigella infection. |
| Keywords | General Biochemistry, Genetics and Molecular Biology |
| Immunology and Microbiology (miscellaneous) | |
| Medicine (miscellaneous) | |
| Neuroscience (miscellaneous) | |
| Article number | dmm050431 |
| Journal | Disease Models and Mechanisms |
| Journal citation | 17 (1) |
| ISSN | 1754-8403 |
| Year | 2024 |
| Publisher | The Company of Biologists |
| Publisher's version | License CC BY 4.0 File Access Level Open (open metadata and files) |
| Digital Object Identifier (DOI) | https://doi.org/10.1242/dmm.050431 |
| Publication dates | |
| Published online | 22 Dec 2023 |
| Published in print | 2024 |
| Project | H2020-MSCA-IF-2015 – 700088 |
| 100229/Z/12/Z | |
| WT097411MA | |
| NA | |
| 772853 - ENTRAPMENT | |
| Funder | European Commission |
| Wellcome Trust | |
| Wellcome Trust | |
| Lister Institute of Preventive Medicine | |
| Wellcome Trust | |
| European Research Council |