Toll-Like Receptor 5-Deficient Mice Have Dysregulated Intestinal Gene Expression and Nonspecific Resistance to Salmonella -Induced Typhoid-Like Disease Article (Web of Science)

abstract

  • ABSTRACT The recognition of flagellin by Toll-like receptor 5 (TLR5) is the dominant means by which model intestinal epithelia activate proinflammatory gene expression in response to Salmonella enterica . The role of the flagellin-TLR5 interaction in vivo has been addressed primarily via studies that use flagellar mutants. Such studies suggest that host recognition of flagellin promotes rapid neutrophil recruitment that protects the host from this pathogen. However, these works do not directly address the role of TLR5 and are subject to the caveat that flagellar mutations may broadly affect Salmonella gene expression. Thus, we examined the role of the flagellin-TLR5 interaction via the use of TLR5-deficient (TLR5KO) mice. We utilized both the traditional model of murine Salmonella infection, wherein low-dose oral infection of mice with Salmonella enterica subsp. enterica serovar Typhimurium results in systemic typhoid-like disease, and a more recently characterized model in which mice are pretreated with streptomycin to result in gut-restricted acute enteritis. In the enteritis model, TLR5KO mice had more severe gut pathology, thus “phenocopying” previous results obtained with Salmonella mutants. In contrast, TLR5KO mice were resistant to Salmonella -induced typhoid-like disease. However, such resistance was not specific for flagellated serovar Typhimurium, but rather, TLR5KO mice were also resistant to challenges by flagellin-deficient serovar Typhimurium. Such resistance associated with elevations in the microbiota was ablated by antibiotic pretreatment and correlated with basal elevations in intestinal host defense gene expression. All together, these results indicate that the resistance of TLR5KO mice to Salmonella -induced typhoid-like illness resulted from alterations in their basal phenotype rather than from the lack of TLR5 ligation during the infection per se.

authors

  • Kumar, Matam Vijay
  • Aitken, Jesse D.
  • Kumar, Amrita
  • Neish, Andrew S.
  • Uematsu, Satoshi
  • Akira, Shizuo
  • Gewirtz, Andrew T.

publication date

  • 2008

webpage

published in

number of pages

  • 5

start page

  • 1276

end page

  • 1281

volume

  • 76

issue

  • 3