title: Stereotyped and specific gene expression programs in human innate immune responses to bacteria.
abstract: The innate immune response is crucial for defense against microbial pathogens. To investigate the molecular choreography of this response, we carried out a systematic examination of the gene expression program in human peripheral blood mononuclear cells responding to bacteria and bacterial products. We found a remarkably stereotyped program of gene expression induced by bacterial lipopolysaccharide and diverse killed bacteria. An intricately choreographed expression program devoted to communication between cells was a prominent feature of the response. Other features suggested a molecular program for commitment of antigen-presenting cells to antigens captured in the context of bacterial infection. Despite the striking similarities, there were qualitative and quantitative differences in the responses to different bacteria. Modulation of this host-response program by bacterial virulence mechanisms was an important source of variation in the response to different bacteria.
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Boldrick
authors.forename: Ash A
authors.initials: AA
authors.lastname: Alizadeh
authors.forename: Maximilian
authors.initials: M
authors.lastname: Diehn
authors.forename: Sandrine
authors.initials: S
authors.lastname: Dudoit
authors.forename: Chih Long
authors.initials: CL
authors.lastname: Liu
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Belcher
authors.forename: David
authors.initials: D
authors.lastname: Botstein
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Brown
authors.forename: David A
authors.initials: DA
authors.lastname: Relman
mesh_terms: D001419:Bacteria / Q000276:immunology* / Q000472:pathogenicity*; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D001886:Bordetella pertussis / Q000276:immunology / Q000472:pathogenicity; D004306:Dose-Response Relationship, Immunologic; D004926:Escherichia coli / Q000276:immunology / Q000472:pathogenicity; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D007109:Immunity / Q000187:drug effects / Q000235:genetics*; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D020411:Oligonucleotide Array Sequence Analysis; D013211:Staphylococcus aureus / Q000276:immunology / Q000472:pathogenicity; D014774:Virulence / Q000276:immunology
chemical_list: D001427:Bacterial Toxins; D008070:Lipopolysaccharides