title: Staphylococcus aureus Infection in Humanized Mice: A New Model to Study Pathogenicity Associated With Human Immune Response.
abstract: 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.
authors: Department of Gynecology and Obstetrics, University Medical Center Regensburg.
authors: Janin
authors: J
authors: Knop
authors: Department of Internal Medicine I, University Hospital Regensburg.
authors: Frank
authors: F
authors: Hanses
authors: Department of Gynecology and Obstetrics, University Medical Center Regensburg.
authors: Teresa
authors: T
authors: Leist
authors: Department of Medicine, University of North Carolina-Chapel Hill.
authors: Nancie M
authors: NM
authors: Archin
authors: Department of Gynecology and Obstetrics, University Medical Center Regensburg.
authors: Stefan
authors: S
authors: Buchholz
authors: Institute for Medical Microbiology and Hygiene, University of Regensburg, Germany.
authors: Joachim
authors: J
authors: Gläsner
authors: Institute for Medical Microbiology and Hygiene, University of Regensburg, Germany.
authors: André
authors: A
authors: Gessner
authors: Department of Gynecology and Obstetrics, University Medical Center Regensburg.
authors: Anja K
authors: AK
authors: Wege
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D053148:Caspase 3 / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000276:immunology* / Q000472:pathogenicity*; D013601:T-Lymphocytes / Q000276:immunology; D014774:Virulence; D019014:fas Receptor / Q000276:immunology
chemical_list: D019014:fas Receptor; D053148:Caspase 3
keywords: Staphylococcus aureus; T-cell apoptosis; caspase-3; fas receptor; humanized mice (HM)