A mouse model for the human pathogen Salmonella typhi.
Salmonella enterica serovar Typhi (S. Typhi) causes typhoid fever, a life-threatening human disease. The lack of animal models due to S. Typhi's strict human host specificity has hindered its study and vaccine development. We find that immunodeficient Rag2(-/-) γc(-/-) mice engrafted with human fetal liver hematopoietic stem and progenitor cells are able to support S. Typhi replication and persistent infection. A S. Typhi mutant in a gene required for virulence in humans was unable to replicate in these mice. Another mutant unable to produce typhoid toxin exhibited increased replication, suggesting a role for this toxin in the establishment of persistent infection. Furthermore, infected animals mounted human innate and adaptive immune responses to S. Typhi, resulting in the production of cytokines and pathogen-specific antibodies. We expect that this mouse model will be a useful resource for understanding S. Typhi pathogenesis and for evaluating potential vaccine candidates against typhoid fever.
Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06520, USA.
Jeongmin
J
Song
Tim
T
Willinger
Anthony
A
Rongvaux
Elizabeth E
EE
Eynon
Sean
S
Stevens
Markus G
MG
Manz
Richard A
RA
Flavell
Jorge E
JE
Galán
D056704:Adaptive Immunity; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D027682:Cation Transport Proteins / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004195:Disease Models, Animal; D006412:Hematopoietic Stem Cells / Q000382:microbiology; D058507:Host Specificity; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D012485:Salmonella typhi / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D014435:Typhoid Fever / Q000276:immunology*; D014774:Virulence; D000099173:Natural Resistance-associated Macrophage Protein 1
D000907:Antibodies, Bacterial; D027682:Cation Transport Proteins; D016207:Cytokines; D000099173:Natural Resistance-associated Macrophage Protein 1