Stereotyped and specific gene expression programs in human innate immune responses to bacteria.
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.
Boldrick
Jennifer C
JC
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Alizadeh
Ash A
AA
Diehn
Maximilian
M
Dudoit
Sandrine
S
Liu
Chih Long
CL
Belcher
Christopher E
CE
Botstein
David
D
Staudt
Louis M
LM
Brown
Patrick O
PO
Relman
David A
DA
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
D001427:Bacterial Toxins; D008070:Lipopolysaccharides