Toll-like receptor-deficient mice reveal how innate immune signaling influences Salmonella virulence strategies

Cell Host Microbe. 2014 Feb 12;15(2):203-13. doi: 10.1016/j.chom.2014.01.013.

Abstract

Pathogens utilize features of the host response as cues to regulate virulence gene expression. Salmonella enterica serovar Typhimurium (ST) sense Toll-like receptor (TLR)-dependent signals to induce Salmonella Pathogenicity Island 2 (SPI2), a locus required for intracellular replication. To examine pathogenicity in the absence of such cues, we evaluated ST virulence in mice lacking all TLR function (Tlr2(-/-)xTlr4(-/-)xUnc93b1(3d/3d)). When delivered systemically to TLR-deficient mice, ST do not require SPI2 and maintain virulence by replicating extracellularly. In contrast, SPI2 mutant ST are highly attenuated after oral infection of the same mice, revealing a role for SPI2 in the earliest stages of infection, even when intracellular replication is not required. This early requirement for SPI2 is abolished in MyD88(-/-)xTRIF(-/-) mice lacking both TLR- and other MyD88-dependent signaling pathways, a potential consequence of compromised intestinal permeability. These results demonstrate how pathogens use plasticity in virulence strategies to respond to different host immune environments.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Host-Pathogen Interactions*
  • Immunity, Innate*
  • Mice
  • Mice, Knockout
  • Salmonella typhimurium / immunology*
  • Salmonella typhimurium / pathogenicity*
  • Signal Transduction*
  • Toll-Like Receptors / deficiency
  • Toll-Like Receptors / immunology*
  • Virulence

Substances

  • Toll-Like Receptors