Staphylococcus aureus Infection in Humanized Mice: A New Model to Study Pathogenicity Associated With Human Immune Response

Background. Staphylococcus aureus is a common pathogen among humans worldwide, with an increasing prevalence of multidrug resistance. The understanding of virulence factors inducing pathogenicity is still incomplete, and thus far the transfer of results from animal studies into successful clinical t...

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Bibliographic Details
Published in:The Journal of infectious diseases 2015-08, Vol.212 (3), p.435-444
Main Authors: Knop, Janin, Hanses, Frank, Leist, Teresa, Archin, Nancie M., Buchholz, Stefan, Gläsner, Joachim, Gessner, André, Wege, Anja K.
Format: Article
Language:English
Subjects:
Animals
Apoptosis - immunology
B-Lymphocytes - immunology
BACTERIA
Caspase 3 - immunology
Cells, Cultured
Disease Models, Animal
fas Receptor - immunology
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells
Humans
Mice
Mice, Transgenic
Staphylococcal Infections - immunology
Staphylococcal Infections - microbiology
Staphylococcus aureus - immunology
Staphylococcus aureus - pathogenicity
T-Lymphocytes - immunology
Virulence
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Summary:Background. Staphylococcus aureus is a common pathogen among humans worldwide, with an increasing prevalence of multidrug resistance. The understanding of virulence factors inducing pathogenicity is still incomplete, and thus far the transfer of results from animal studies into successful clinical trials has been difficult. Methods. In this study, we established an S. aureus infection model in mice engrafted with a human immune system, compared it with infected wild-type and nonhumanized mice, and investigated pathogenesis in these models. Results. Staphylococcus aureus infection was aggravated in humanized mice, compared with wild-type or nonengrafted mice. The humanized mice displayed a significantly reduced survival percentage, increased weight loss, and a more-rapid increase in bacterial burden. In addition, S. aureus infection induced T-cell activation, apoptosis, and Fas receptor expression in humanized but not wild-type mice. Conclusions. Our findings demonstrate the different pathogenetic mechanisms in wild-type and humanized mice and the possible benefit of including humanized mice in future studies involving S. aureus as a prior step to human clinical trials.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiv073