title: Expression of genes encoding innate host defense molecules in normal human monocytes in response to Candida albicans.
abstract: Little is known about the regulation and coordinated expression of genes involved in the innate host response to Candida albicans. We therefore examined the kinetic profile of gene expression of innate host defense molecules in normal human monocytes infected with C. albicans using microarray technology. Freshly isolated peripheral blood monocytes from five healthy donors were incubated with C. albicans for 0 to 18 h in parallel with time-matched uninfected control cells. RNA from monocytes was extracted and amplified for microarray analysis, using a 42,421-gene cDNA chip. Expression of genes encoding proinflammatory cytokines, including tumor necrosis factor alpha, interleukin 1 (IL-1), IL-6, and leukemia inhibitory factor, was markedly enhanced during the first 6 h and coincided with an increase in phagocytosis. Expression of these genes returned to near baseline by 18 h. Genes encoding chemokines, including IL-8; macrophage inflammatory proteins 1, 3, and 4; and monocyte chemoattractant protein 1, also were strongly up-regulated, with peak expression at 4 to 6 h, as were genes encoding chemokine receptors CCR1, CCR5, CCR7, and CXCR5. Expression of genes whose products may protect monocyte viability, such as BCL2-related protein, metallothioneins, CD71, and SOCS3, was up-regulated at 4 to 6 h and remained elevated throughout the 18-h time course. On the other hand, expression of genes encoding T-cell-regulatory molecules (e.g., IL-12, gamma interferon, and transforming growth factor beta) was not significantly affected during the 18-h incubation. Moreover, genes encoding IL-15, the IL-13 receptor (IL-13Ra1), and CD14 were suppressed during the 18-h exposure to C. albicans. Thus, C. albicans is a potent inducer of a dynamic cascade of expression of genes whose products are related to the recruitment, activation, and protection of neutrophils and monocytes.
authors.affiliation: Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute/NIH, Room 1-5740, Bethesda, MD 20892, USA.
authors.forename: Hee Sup
authors.initials: HS
authors.lastname: Kim
authors.forename: Eun Hwa
authors.initials: EH
authors.lastname: Choi
authors.forename: Javed
authors.initials: J
authors.lastname: Khan
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Roilides
authors.forename: Andrea
authors.initials: A
authors.lastname: Francesconi
authors.forename: Miki
authors.initials: M
authors.lastname: Kasai
authors.forename: Tin
authors.initials: T
authors.lastname: Sein
authors.forename: Robert L
authors.initials: RL
authors.lastname: Schaufele
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sakurai
authors.forename: Chang Gue
authors.initials: CG
authors.lastname: Son
authors.forename: Braden T
authors.initials: BT
authors.lastname: Greer
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Caron A
authors.initials: CA
authors.lastname: Lyman
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Walsh
mesh_terms: D015703:Antigens, CD / Q000235:genetics; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics; D002176:Candida albicans / Q000276:immunology*; D018925:Chemokines / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics; D019409:Interleukin-15 / Q000235:genetics; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000235:genetics; D008668:Metallothionein / Q000235:genetics; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics; D011990:Receptors, Transferrin; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C068126:CD71 antigen; D018925:Chemokines; C508840:IL23A protein, human; D019409:Interleukin-15; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019707:Receptors, Chemokine; D011990:Receptors, Transferrin; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D008668:Metallothionein