Lipopolysaccharides belonging to different Salmonella serovars are differentially capable of activating Toll-like receptor 4

Infect Immun. 2014 Nov;82(11):4553-62. doi: 10.1128/IAI.02297-14. Epub 2014 Aug 18.

Abstract

Salmonella enterica subsp. enterica serovar (serotype) Abortusovis is a member of the Enterobacteriaceae. This serotype is naturally restricted to ovine species and does not infect humans. Limited information is available about the immune response of sheep to S. Abortusovis. S. Abortusovis, like Salmonella enterica subsp. enterica serovar Typhi, causes a systemic infection in which, under natural conditions, animals are not able to raise a rapid immune response. Failure to induce the appropriate response allows pathogens to reach the placenta and results in an abortion. Lipopolysaccharides (LPSs) are pathogen-associated molecular patterns (PAMPs) that are specific to bacteria and are not synthesized by the host. Toll-like receptors (TLRs) are a family of receptors that specifically recognize PAMPs. As a first step, we were able to identify the presence of Toll-like receptor 4 (TLR4) on the ovine placenta by using an immunohistochemistry technique. To our knowledge, this is the first work describing the interaction between S. Abortusovis LPS and TLR4. Experiments using an embryonic cell line (HEK293) transfected with human and ovine TLR4s showed a reduction of interleukin 8 (IL-8) production by S. Abortusovis and Salmonella enterica subsp. enterica serovar Paratyphi upon LPS stimulation compared to Salmonella enterica subsp. enterica serovar Typhimurium. Identical results were observed using heat-killed bacteria instead of LPS. Based on data obtained with TLR4 in vitro stimulation, we demonstrated that the serotype S. Abortusovis is able to successfully evade the immune system whereas S. Typhimurium and other serovars fail to do so.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Cloning, Molecular
  • Female
  • Gene Expression Regulation / physiology
  • HEK293 Cells
  • Humans
  • Lipopolysaccharides / classification*
  • Lipopolysaccharides / immunology*
  • Placenta / cytology
  • Placenta / metabolism
  • Pregnancy
  • Salmonella / classification*
  • Sheep
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Bacterial Proteins
  • Lipopolysaccharides
  • Toll-Like Receptor 4