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A Mouse Model for the Human Pathogen Salmonella Typhi
Open accessAbstract
SUMMARY Salmonella enterica serovar Typhi (S. Typhi) is the cause of typhoid fever, a life-threatening disease of humans. The lack of an animal model due to S. typhi's strict human host specificity has been a significant obstacle in the understanding of its pathogenesis and the development of a safe and effective vaccine against typhoid fever. We report here the development of a mouse model for S. Typhi infection. We showed that immunodeficient Rag2 -/- γc -/- mice engrafted with human fetal liver hematopoietic stem and progenitor cells were able to support S. Typhi replication and persistent infection. A S. Typhi strain carrying a mutation in a gene required for its virulence in humans was not able to replicate in these humanized mice. In contrast, another mutant strain unable to produce the recently identified typhoid toxin, exhibited increased replication suggesting a potential role for this toxin in the establishment of persistent infection. Furthermore, infected animals mounted a human innate and adaptive immune response to S. Typhi resulting in the production of cytokines and pathogen-specific antibodies. These results therefore indicate that this animal model can be used to study S. Typhi pathogenesis and to evaluate potential vaccine candidates against typhoid fever.
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Parry, C. M., Hien, T. T., Dougan, G., White, N. J., & Farrar, J. J. (2002) · New England Journal of Medicine · doi:10.1056/nejmra020201 · Cited by 1,112
Monack, D. M., Bouley, D. M., & Falkow, S. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20031319 · Cited by 396
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Dougan, G., & Baker, S. (2014) · Annual Review of Microbiology · doi:10.1146/annurev-micro-091313-103739 · Cited by 338
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Wong, C. K., Yusta, B., Koehler, J. A., Baggio, L. L., McLean, B. A., Matthews, D., Seeley, R. J., & Drucker, D. J. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.08.003 · Cited by 138
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Metadata
- Authors
- Song, J., Willinger, T., Rongvaux, A., Eynon, E. E., Stevens, S., Manz, M. G., Flavell, R. A., & Galán, J. E.
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 8
- Issue
- 4
- Pages
- 369-376
- ISSN
- 1931-3128 (ISSN-L)
- OpenAlex
- W2146288137
- Cited by
- 202
- References
- 2
- FWCI
- 21.76
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Song, J., Willinger, T., Rongvaux, A., Eynon, E. E., Stevens, S., Manz, M. G., Flavell, R. A., & Galán, J. E. (2010). A Mouse Model for the Human Pathogen Salmonella Typhi. Cell Host & Microbe. https://doi.org/10.1016/j.chom.2010.09.003
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