A mouse model of Salmonella typhi infection

Cell. 2012 Oct 26;151(3):590-602. doi: 10.1016/j.cell.2012.08.042.

Abstract

Salmonella spp. are gram-negative flagellated bacteria that can cause food- and waterborne gastroenteritis and typhoid fever in humans. We now report that flagellin from Salmonella spp. is recognized in mouse intestine by Toll-like receptor 11 (TLR11). Absence of TLR11 renders mice more susceptible to infection by S. Typhimurium, with increased dissemination of the bacteria and enhanced lethality. Unlike S. Typhimurium, S. Typhi, a human obligatory pathogen that causes typhoid fever, is normally unable to infect mice. TLR11 is expressed in mice, but not in humans, and remarkably, we find that tlr11(-/-) mice are efficiently infected with orally administered S. Typhi. We also find that tlr11(-/-) mice can be immunized against S. Typhi. Therefore, tlr11(-/-) mice represent a small-animal model for the study of the immune response to S. Typhi and for the development of vaccines against this important human pathogen.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Flagellin / metabolism
  • Host-Pathogen Interactions*
  • Humans
  • Mice*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Salmonella typhi*
  • Species Specificity
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / immunology
  • Toll-Like Receptors / metabolism
  • Typhoid Fever / immunology*
  • Typhoid Fever / microbiology*

Substances

  • Tlr11 protein, mouse
  • Toll-Like Receptors
  • Flagellin