title: CD14, a key candidate gene associated with a specific immune response to cockroach.
abstract: BACKGROUND
  Sensitization to cockroach allergen is one of the strongest predictors of asthma morbidity, especially among African Americans.
  
  
  OBJECTIVE
  Our aims were to determine the genomic basis of cockroach sensitization and the specific response to cockroach antigen.
  
  
  METHODS
  We investigated the Th1/Th2 cytokine profile of co-cultured plasmacytoid dendritic cells (pDCs) and CD4+ T cells and the 'transcript signature' of the immune response to cockroach antigen using high-throughput expression profiling of co-cultured cells.
  
  
  RESULTS
  We observed significantly elevated levels of IL-13, IL-10, and TNF-alpha, but undetectable levels of IL-12p70 and IFN-alpha, when cultures were exposed to crude cockroach antigen. A significant difference was observed for IL-13 between cockroach-allergic and non-allergic individuals (P=0.039). Microarray analyses demonstrated a greater response at 48 h compared with 4 h, with 50 genes being uniquely expressed in cockroach antigen-treated cells, including CD14, S100A8, CCL8, and IFI44L. The increased CD14 expression was further observed in purified pDCs, human monocytic THP-1 cells, and the supernatant of co-cultured pDCs and CD4+ T cells on exposure to cockroach extract. Furthermore, the most differential expression of CD14 between cockroach allergy and non-cockroach allergy was only observed among individuals with the CC 'high-risk' genotype of the CD14-260C/T. Ingenuity Pathways Analysis analyses suggested the IFN signalling as the most significant canonical pathway.
  
  
  CONCLUSIONS
  Our results suggest that these differentially expressed genes, particularly CD14, and genes in the IFN signalling pathway may be important candidates for further investigation of their role in the immune response to cockroach allergen.
authors.affiliation: Department of Medicine, Division of Allergy and Clinical Immunology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: P
authors.initials: P
authors.lastname: Gao
authors.forename: D N
authors.initials: DN
authors.lastname: Grigoryev
authors.forename: N M
authors.initials: NM
authors.lastname: Rafaels
authors.forename: D
authors.initials: D
authors.lastname: Mu
authors.forename: J M
authors.initials: JM
authors.lastname: Wright
authors.forename: C
authors.initials: C
authors.lastname: Cheadle
authors.forename: A
authors.initials: A
authors.lastname: Togias
authors.forename: T H
authors.initials: TH
authors.lastname: Beaty
authors.forename: R A
authors.initials: RA
authors.lastname: Mathias
authors.forename: J T
authors.initials: JT
authors.lastname: Schroeder
authors.forename: K C
authors.initials: KC
authors.lastname: Barnes
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003058:Cockroaches / Q000276:immunology*; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology* / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008875:Middle Aged; D018418:Th2 Cells
chemical_list: D000485:Allergens; D016207:Cytokines; D016898:Interferon-alpha; D018950:Lipopolysaccharide Receptors