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Humanized mice are susceptible to Salmonella typhi infection

Cellular & Molecular Immunology volume 8, pages 83–87 (2011)Cite this article

Abstract

Salmonella enterica serovar Typhi is a pathogen that only infects humans. Currently, there is no animal model for studying this pathogen. Recently, alymphoid RAG-2−/−/γc−/− mice engrafted with human leukocytes, known as humanized mice, have been successfully utilized to develop experimental models for several human-specific viral infections, including HIV, human-like dengue fever and hepatitis C virus. Little is known about the usefulness and feasibility of the humanized mouse model for the study of human-specific bacterial pathogens, such as S. typhi. The aim of this study was to determine if Salmonella enterica serovar Typhi could establish productive infection in humanized mice. Here we report that intravenous inoculation of S. typhi into humanized mice, but not controls, established S. typhi infections. High bacterial loads were found in the liver, spleen, blood and bone marrow of mice reconstituted with human leukocytes, but not in the unreconstituted control mice. Importantly, S. typhi-infected humanized mice lost significant body weight, and some of the infected mice displayed neurological symptoms. Our data suggest, for the first time, that humanized mice are susceptible to S. typhi challenge and that this model can be utilized to study the pathogenesis of S. typhi to develop novel therapeutic strategies.

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Acknowledgements

We are thankful to Dr Brain Coombes, McMaster University, Canada, for providing us with Salmonella typhi and for helpful discussions. This study was supported by a grant from CIHR to Ali A Ashkar. AAA is a recipient of a Career Award in Health Sciences from Rx&D/CIHR.

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  1. M Firoz Mian and Elisabeth A Pek: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology and Molecular Medicine, Institute for Infectious Disease Research, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada

    M Firoz Mian, Elisabeth A Pek, Meghan J Chenoweth & Ali A Ashkar

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  1. M Firoz Mian
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  2. Elisabeth A Pek
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  3. Meghan J Chenoweth
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  4. Ali A Ashkar
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Correspondence to Ali A Ashkar.

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Firoz Mian, M., Pek, E., Chenoweth, M. et al. Humanized mice are susceptible to Salmonella typhi infection. Cell Mol Immunol 8, 83–87 (2011). https://doi.org/10.1038/cmi.2010.52

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