Salmonella typhimurium-induced M1 macrophage polarization is dependent on the bacterial O antigen

World J Microbiol Biotechnol. 2016 Feb;32(2):22. doi: 10.1007/s11274-015-1978-z. Epub 2016 Jan 8.


Recently, macrophages were shown to be capable of differentiating toward two phenotypes after antigen stimulation: a classically activated (M1) or an alternatively activated phenotype (M2). To investigate the effect of Salmonella enteric serovar typhimurium (S. typhimurium) on macrophage differentiation, we compared macrophage phenotypes after infection of murine bone marrow-derived macrophages with wild-type S. typhimurium and its isogenic rfc mutant. S. typhimurium C5 induced M1 macrophage polarization and enhanced inducible nitric oxide synthase expression by macrophages; this induction was dependent on Toll-like receptor 4. In contrast, the Δrfc mutant (S. typhimurium C5 rfc::Km(r)) lost this function and induced an M2 response in the macrophages. Here, we propose that S. typhimurium C5 is capable of polarizing macrophages towards the M1 phenotype and that this polarization is dependent on the O antigen encoded by rfc. Our finding indicates that M1 macrophage polarization induced by S. typhimurium may be related to the ability of this intracellular bacterium to survive and replicate within macrophages, which is essential for systemic disease.

Keywords: Macrophage polarization; O antigen; Salmonella typhimurium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Cytokines / immunology
  • Gene Deletion
  • Hexosyltransferases / genetics
  • Hexosyltransferases / immunology
  • Host-Pathogen Interactions
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / microbiology*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / immunology
  • O Antigens / genetics
  • O Antigens / immunology*
  • O Antigens / isolation & purification
  • Phenotype
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / immunology*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology


  • Cytokines
  • O Antigens
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Nitric Oxide Synthase Type II
  • Hexosyltransferases
  • O-antigen polymerase