Humanized nonobese diabetic-scid IL2rgammanull mice are susceptible to lethal Salmonella Typhi infection.
Document Type
Article
Publication Date
2010
Keywords
Animals-Newborn, Antigens-CD45, Cytokines, Flow-Cytometry, Hematopoietic-Stem-Cell-Transplantation, Hematopoietic-Stem-Cells, Interferon-gamma, Interleukin-Receptor-Common-gamma-Subunit, Mice-Inbred-C57BL, Mice-Inbred-NOD, Mice-Knockout, Mice-SCID, Salmonella-typhi, Tumor-Necrosis-Factor-alpha, Typhoid-Fever, Virulence
First Page
15589
Last Page
15594
JAX Source
Proc Natl Acad Sci U S A 2010 Aug; 107(35):15589-94.
Abstract
Salmonella enterica serovar Typhi, the cause of typhoid fever, is host-adapted to humans and unable to cause disease in mice. Here, we show that S. Typhi can replicate in vivo in nonobese diabetic (NOD)-scid IL2rgamma(null) mice engrafted with human hematopoietic stem cells (hu-SRC-SCID mice) to cause a lethal infection with pathological and inflammatory cytokine responses resembling human typhoid. In contrast, S. Typhi does not exhibit net replication or cause illness in nonengrafted or immunocompetent control animals. Screening of transposon pools in hu-SRC-SCID mice revealed both known and previously unknown Salmonella virulence determinants, including Salmonella Pathogenicity Islands 1, 2, 3, 4, and 6. Our observations indicate that the presence of human immune cells allows the in vivo replication of S. Typhi in mice. The hu-SRC-SCID mouse provides an unprecedented opportunity to gain insights into S. Typhi pathogenesis and devise strategies for the prevention of typhoid fever.
Recommended Citation
Libby SJ,
Brehm MA,
Greiner DL,
Shultz LD,
McClelland M,
Smith KD,
Cummings LA,
et a.
Humanized nonobese diabetic-scid IL2rgammanull mice are susceptible to lethal Salmonella Typhi infection. Proc Natl Acad Sci U S A 2010 Aug; 107(35):15589-94.