Lipopolysaccharides Belonging to Different Salmonella Serovars Are Differentially Capable of Activating Toll-Like Receptor 4

Abstract

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.