Salmonella typhimurium infection and lipopolysaccharide stimulation inducesimilar changes in macrophage gene expression

Changes in macrophage phenotype induced during infection result from the re cognition of bacterial products as well as the action of bacterial virulenc e factors. We used the unprecedented opportunity provided hy gene arrays to simultaneously study the expression of hundreds of genes during Salmonella typhimurium infection of macrophages and to assess the contribution of the bacterial virulence factor, LPS, in initiating the host responses to Salmo nella, We found that S, typhimurium infection caused significant changes in the expression of numerous genes encoding chemokines, cell surface recepto rs, signaling molecules, and transcriptional activators at 4 h postinfectio n of the RAW 264.7 murine macrophage cell line. Our results revealed change s in the expression of several genes that had not been previously implicate d in the host responses to S, typhimurium infection, as well as changes in the expression of several genes previously shown to be regulated by S, typh imurium infection. An overlapping spectrum of genes was expressed in respon se to virulent S, typhimurium and purified S, typhimurium LPS, reinforcing the major role of this surface molecule in stimulating the early response o f macrophages to bacterial infection. The macrophage gene expression profil e was further altered by activation with IFN-gamma, indicating that host ce ll responses depend on the activation state of the cell.