title: Salmonella typhimurium-induced M1 macrophage polarization is dependent on the bacterial O antigen.
abstract: 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.
authors.affiliation: State Key Laboratory of Virology, Medical Research Institute of Wuhan University and Department of Immunology and Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Medicine, Donghu Road 185#, Wuhan, 430071, Hubei Province, China.
authors.forename: Fengling
authors.initials: F
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Virology, Medical Research Institute of Wuhan University and Department of Immunology and Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Medicine, Donghu Road 185#, Wuhan, 430071, Hubei Province, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Virology, Medical Research Institute of Wuhan University and Department of Immunology and Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Medicine, Donghu Road 185#, Wuhan, 430071, Hubei Province, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Qu
authors.affiliation: State Key Laboratory of Virology, Medical Research Institute of Wuhan University and Department of Immunology and Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Medicine, Donghu Road 185#, Wuhan, 430071, Hubei Province, China. zhangxiaolian@whu.edu.cn.
authors.forename: Xiaolian
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D017353:Gene Deletion; D006602:Hexosyltransferases / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D019081:O Antigens / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D010641:Phenotype; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; D019081:O Antigens; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D052247:Nitric Oxide Synthase Type II; D006602:Hexosyltransferases; C085652:O-antigen polymerase
keywords: Macrophage polarization; O antigen; Salmonella typhimurium