Mast cells, which interact with Escherichia coli, up-regulate genes associated with innate immunity and become less responsive to Fc(epsilon)RI-mediated activation.
Mast cells, which are associated with T helper cell type 2-dependent inflammation, have now been implicated in the innate immune response. To further characterize how mast cells are programmed to respond to infectious organisms, we used expression profiling using DNA microarray analysis of gene expression by human mast cells (huMC) during ingestion of Escherichia coli and examined immunoglobulin E (IgE)-mediated degranulation. Analysis of data revealed that specific groups of genes were modulated, including genes encoding transcription factors, cell signaling molecules, cell cycle regulators, enzymes, cytokines, novel chemokines of the CC family, adhesion molecules, and costimulatory molecules. Enzyme-linked immunosorbent assay analysis confirmed the production of tumor necrosis factor and the chemokines CC chemokine ligand (CCL)-1/I-309, CCL-19/macrophage-inflammatory protein-3beta (MIP-3beta), and CCL-18/MIP-4; flow cytometry confirmed the up-regulation of carcinoembryonic antigen-related cell adhesion molecule 1, the integrin CD49d, and CD80. Coincubation with E. coli down-regulated Fc receptor for IgE I (FcepsilonRI) expression and FcepsilonRI-mediated huMC degranulation. These data are consistent with the concept that bacterial exposure directs mast cell responses toward innate immunity and away from IgE-mediated effects.
Kulka
Marianna
M
Allergy-Immunology Division, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Fukuishi
Nobuyuki
N
Rottem
Menachem
M
Mekori
Yoseph A
YA
Metcalfe
Dean D
DD
D015815:Cell Adhesion Molecules / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007073:Immunoglobulin E / Q000276:immunology; D008407:Mast Cells / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D015815:Cell Adhesion Molecules; D018925:Chemokines; D012333:RNA, Messenger; D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E