title: Humanized mice are susceptible to Salmonella typhi infection.
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(-/-)/γ(c)(-/-) 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.
authors.affiliation: Institute for Infectious Disease Research, Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Firoz Mian
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Pek
authors.forename: Meghan J
authors.initials: MJ
authors.lastname: Chenoweth
authors.forename: Ali A
authors.initials: AA
authors.lastname: Ashkar
mesh_terms: D000818:Animals; D058491:Bacterial Load / Q000276:immunology; D001835:Body Weight; D004268:DNA-Binding Proteins / Q000276:immunology; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D005333:Fetus; D018380:Hematopoietic Stem Cell Transplantation; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007275:Injections, Intravenous; D017493:Leukocyte Common Antigens / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic / Q000276:immunology*; D012485:Salmonella typhi / Q000276:immunology / Q000472:pathogenicity; D013045:Species Specificity; D014435:Typhoid Fever / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015431:Weight Loss; D014916:Whole-Body Irradiation
chemical_list: D004268:DNA-Binding Proteins; C064655:V(D)J recombination activating protein 2; D017493:Leukocyte Common Antigens