CD14, a key candidate gene associated with a specific immune response to cockroach
P. Gao
Departments of Medicine, Division of Allergy and Clinical Immunology
Search for more papers by this authorD. N. Grigoryev
Departments of Medicine, Division of Allergy and Clinical Immunology
Search for more papers by this authorN. M. Rafaels
Departments of Medicine, Division of Allergy and Clinical Immunology
Search for more papers by this authorD. Mu
Departments of Medicine, Division of Allergy and Clinical Immunology
Search for more papers by this authorC. Cheadle
Departments of Medicine, Division of Allergy and Clinical Immunology
Search for more papers by this authorA. Togias
Departments of Medicine, Division of Allergy and Clinical Immunology
Search for more papers by this authorR. A. Mathias
Departments of Medicine, Division of Allergy and Clinical Immunology
Medicine, Division of General Internal Medicine, The Johns Hopkins University, Baltimore, MD, USA
Search for more papers by this authorJ. T. Schroeder
Departments of Medicine, Division of Allergy and Clinical Immunology
Search for more papers by this authorK. C. Barnes
Departments of Medicine, Division of Allergy and Clinical Immunology
Search for more papers by this authorP. Gao
Departments of Medicine, Division of Allergy and Clinical Immunology
Search for more papers by this authorD. N. Grigoryev
Departments of Medicine, Division of Allergy and Clinical Immunology
Search for more papers by this authorN. M. Rafaels
Departments of Medicine, Division of Allergy and Clinical Immunology
Search for more papers by this authorD. Mu
Departments of Medicine, Division of Allergy and Clinical Immunology
Search for more papers by this authorC. Cheadle
Departments of Medicine, Division of Allergy and Clinical Immunology
Search for more papers by this authorA. Togias
Departments of Medicine, Division of Allergy and Clinical Immunology
Search for more papers by this authorR. A. Mathias
Departments of Medicine, Division of Allergy and Clinical Immunology
Medicine, Division of General Internal Medicine, The Johns Hopkins University, Baltimore, MD, USA
Search for more papers by this authorJ. T. Schroeder
Departments of Medicine, Division of Allergy and Clinical Immunology
Search for more papers by this authorK. C. Barnes
Departments of Medicine, Division of Allergy and Clinical Immunology
Search for more papers by this authorSummary
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-α, but undetectable levels of IL-12p70 and IFN-α, 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.
Conclusion 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.
Cite this as: P. Gao, D. N. Grigoryev, N. M. Rafaels, D. Mu, J. M. Wright, C. Cheadle, A. Togias, T. H. Beaty, R. A. Mathias, J. T. Schroeder and K. C. Barnes, Clinical & Experimental Allergy, 2010 (40) 1353–1364.
Supporting Information
Figure S1. The levels of TNF-α were detected by ELISA in the supernatant of cultured human pDCs of cockroach sensitized subjects (N=3) in the presence of medium alone and different concentrations of cockroach extract and/or poly-IC (50 μg/mL).
Figure S2. RT-PCR confirmed that human monocytic cells (THP-1) show similar patterns when compared with co-cultured pDCs and CD4+ T cells after cells were exposed to cockroach allergen (100 μL/mL) for 48 h. The most up-regulated was noted for seven of eight genes evaluated in cockroach allergen extract-treated cells as compared to those treated with LPS (100 ng/mL) and Bermuda grass extract (100 μg/mL). Data represent mean fold changes of three experiments.
Table SI. Demographic characteristics of African American atopic participants with and without cockroach sensitization.
Table S2. Clinical characteristics of the African American subjects for genetic association study.
Please note: Wiley-Blackwell is not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article.
| Filename | Description |
|---|---|
| CEA_3561_sm_supplinfo.pdf62.1 KB | Supporting info item |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1 Salo PM, Arbes SJ Jr, Crockett PW, Thorne PS, Cohn RD, Zeldin DC. Exposure to multiple indoor allergens in US homes and its relationship to asthma. J Allergy Clin Immunol 2008; 121: 678–84, e2.
- 2 Pomes A. Intrinsic properties of allergens and environmental exposure as determinants of allergenicity. Allergy 2002; 57: 673–9.
- 3 Rosenstreich DL, Eggleston P, Kattan M et al. The role of cockroach allergy and exposure to cockroach allergen in causing morbidity among inner-city children with asthma. N Engl J Med 1997; 336: 1356–63.
- 4 Leaderer BP, Belanger K, Triche E et al. Dust mite, cockroach, cat, and dog allergen concentrations in homes of asthmatic children in the northeastern United States: impact of socioeconomic factors and population density. Environ Health Perspect 2002; 110: 419–25.
- 5 Helm RM, Squillace DL, Jones RT, Brenner RJ. Shared allergenic activity in Asian (Blattella asahinai), German (Blattella germanica), American (Periplaneta americana), and Oriental (Blatta orientalis) cockroach species. Int Arch Allergy Appl Immunol 1990; 92: 154–61.
- 6 Ledford DK. Indoor allergens. J Allergy Clin Immunol 1994; 94 (Part 2): 327–34.
- 7 Sporik R, Squillace SP, Ingram JM, Rakes G, Honsinger RW, Platts-Mills TA. Mite, cat, and cockroach exposure, allergen sensitisation, and asthma in children: a case–control study of three schools. Thorax 1999; 54: 675–80.
- 8 Wunschmann S, Gustchina A, Chapman MD, Pomes A. Cockroach allergen Bla g 2: an unusual aspartic proteinase. J Allergy Clin Immunol 2005; 116: 140–5.
- 9 Pomes A, Chapman MD, Vailes LD, Blundell TL, Dhanaraj V. Cockroach allergen Bla g 2: structure, function, and implications for allergic sensitization. Am J Respir Crit Care Med 2002; 165: 391–7.
- 10 Togias A, Horowitz E, Joyner D, Guydon L, Malveaux F. Evaluating the factors that relate to asthma severity in adolescents. Int Arch Allergy Immunol 1997; 113: 87–95.
- 11 Banchereau J, Briere F, Caux C et al. Immunobiology of dendritic cells. Annu Rev Immunol 2000; 18: 767–811.
- 12 Guermonprez P, Valladeau J, Zitvogel L, Thery C, Amigorena S. Antigen presentation and T cell stimulation by dendritic cells. Annu Rev Immunol 2002; 20: 621–67.
- 13 Bratke K, Lommatzsch M, Julius P et al. Dendritic cell subsets in human bronchoalveolar lavage fluid after segmental allergen challenge. Thorax 2007; 62: 168–75.
- 14 Masten BJ, Olson GK, Tarleton CA et al. Characterization of myeloid and plasmacytoid dendritic cells in human lung. J Immunol 2006; 177: 7784–93.
- 15 Upham JW, Zhang G, Rate A et al. Plasmacytoid dendritic cells during infancy are inversely associated with childhood respiratory tract infections and wheezing. J Allergy Clin Immunol 2009; 124: 707–13, e2.
- 16 Wohlfahrt JG, Kunzmann S, Menz G et al. T cell phenotype in allergic asthma and atopic dermatitis. Int Arch Allergy Immunol 2003; 131: 272–82.
- 17 Hansel NN, Cheadle C, Diette GB et al. Analysis of CD4+ T-cell gene expression in allergic subjects using two different microarray platforms. Allergy 2008; 63: 366–9.
- 18 Ketloy C, Engering A, Srichairatanakul U et al. Expression and function of Toll-like receptors on dendritic cells and other antigen presenting cells from non-human primates. Vet Immunol Immunopathol 2008; 125: 18–30.
- 19 Schroeder JT, Bieneman AP, Xiao H et al. TLR9- and FcepsilonRI-mediated responses oppose one another in plasmacytoid dendritic cells by down-regulating receptor expression. J Immunol 2005; 175: 5724–31.
- 20 Moseman EA, Liang X, Dawson AJ et al. Human plasmacytoid dendritic cells activated by CpG oligodeoxynucleotides induce the generation of CD4+ CD25+ regulatory T cells. J Immunol 2004; 173: 4433–42.
- 21 Fonteneau JF, Larsson M, Beignon AS et al. Human immunodeficiency virus type 1 activates plasmacytoid dendritic cells and concomitantly induces the bystander maturation of myeloid dendritic cells. J Virol 2004; 78: 5223–32.
- 22 Grigoryev DN, Mathai SC, Fisher MR et al. Identification of candidate genes in scleroderma-related pulmonary arterial hypertension. Translational Res 2008; 151: 197–207.
- 23 Grigoryev DN, Howell MD, Watkins TN et al. Vaccinia virus-specific molecular signature in atopic dermatitis skin. J Allergy Clin Immunol 2010; 125: 153–9, e28.
- 24 Gao PS, Shimizu K, Grant AV et al. Polymorphisms in the sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) gene are associated with susceptibility to asthma. Eur J Hum Genet 2010; 18: 713–9.
- 25 Harris ML, Darrah E, Lam GK et al. Association of autoimmunity to peptidyl arginine deiminase type 4 with genotype and disease severity in rheumatoid arthritis. Arthritis Rheum 2008; 58: 1958–67.
- 26 Purcell S, Neale B, Todd-Brown K et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007; 81: 559–75.
- 27 Gao PS, Rafaels NM, Hand T et al. Filaggrin mutations that confer risk of atopic dermatitis confer greater risk for eczema herpeticum. J Allergy Clin Immunol 2009; 124: 507–13, 513 e1–7.
- 28 LeVan TD, Bloom JW, Bailey TJ et al. A common single nucleotide polymorphism in the CD14 promoter decreases the affinity of Sp protein binding and enhances transcriptional activity. J Immunol 2001; 167: 5838–44.
- 29 Zambelli-Weiner A, Ehrlich E, Stockton ML et al. Evaluation of the CD14/−260 polymorphism and house dust endotoxin exposure in the Barbados Asthma Genetics Study. J Allergy Clin Immunol 2005; 115: 1203–9.
- 30 Bellinghausen I, Brand U, Knop J, Saloga J. Comparison of allergen-stimulated dendritic cells from atopic and nonatopic donors dissecting their effect on autologous naive and memory T helper cells of such donors. J Allergy Clin Immunol 2000; 105: 988–96.
- 31 Hammad H, Lambrecht BN. Recent progress in the biology of airway dendritic cells and implications for understanding the regulation of asthmatic inflammation. J Allergy Clin Immunol 2006; 118: 331–6.
- 32 Lipscomb MF, Masten BJ. Dendritic cells: immune regulators in health and disease. Physiol Rev 2002; 82: 97–130.
- 33 Charbonnier AS, Hammad H, Gosset P et al. Der p 1-pulsed myeloid and plasmacytoid dendritic cells from house dust mite-sensitized allergic patients dysregulate the T cell response. J Leukocyte Biol 2003; 73: 91–9.
- 34 Kadowaki N. The divergence and interplay between pDC and mDC in humans. Front Biosci 2009; 14: 808–17.
- 35
Wills-Karp M,
Luyimbazi J,
Xu X et al. Interleukin-13: central mediator of allergic asthma.
Science
1998; 282: 2258–61.
10.1038/286264a0 Google Scholar
- 36 Zhu Z, Homer RJ, Wang Z et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest 1999; 103: 779–88.
- 37 Hammad H, Charbonnier AS, Duez C et al. Th2 polarization by Der p 1-pulsed monocyte-derived dendritic cells is due to the allergic status of the donors. Blood 2001; 98: 1135–41.
- 38 Ghaemmaghami AM, Gough L, Sewell HF, Shakib F. The proteolytic activity of the major dust mite allergen Der p 1 conditions dendritic cells to produce less interleukin-12: allergen-induced Th2 bias determined at the dendritic cell level. Clin Exp Allergy 2002; 32: 1468–75.
- 39 Cobb JP, Mindrinos MN, Miller-Graziano C et al. Application of genome-wide expression analysis to human health and disease. Proc Natl Acad Sci USA 2005; 102: 4801–6.
- 40 Xin Y, Yu L, Chen Z et al. Cloning, expression patterns, and chromosome localization of three human and two mouse homologues of GABA(A) receptor-associated protein. Genomics 2001; 74: 408–13.
- 41 Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 1990; 249: 1431–3.
- 42 Dentener MA, Bazil V, Von Asmuth EJ, Ceska M, Buurman WA. Involvement of CD14 in lipopolysaccharide-induced tumor necrosis factor-alpha, IL-6 and IL-8 release by human monocytes and alveolar macrophages. J Immunol 1993; 150: 2885–91.
- 43 Virchow JC Jr, Julius P, Matthys H, Kroegel C, Luttmann W. CD14 expression and soluble CD14 after segmental allergen provocation in atopic asthma. Eur Respir J 1998; 11: 317–23.
- 44 Woo JG, Assa'ad A, Heizer AB, Bernstein JA, Hershey GK. The −159 C→T polymorphism of CD14 is associated with nonatopic asthma and food allergy. J Allergy Clin Immunol 2003; 112: 438–44.
- 45 Ober C, Tsalenko A, Parry R, Cox NJ. A second-generation genomewide screen for asthma-susceptibility alleles in a founder population. Am J Hum Genet 2000; 67: 1154–62.
- 46 Baldini M, Lohman IC, Halonen M, Erickson RP, Holt PG, Martinez FD. A Polymorphism in the 5′ flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E. Am J Respir Cell Mol Biol 1999; 20: 976–83.
- 47 Jackola DR, Basu S, Liebeler CL et al. CD14 promoter polymorphisms in atopic families: implications for modulated allergen-specific immunoglobulin E and G1 responses. Int Arch Allergy Immunol 2006; 139: 217–24.
- 48 Colonna M, Trinchieri G, Liu YJ. Plasmacytoid dendritic cells in immunity. Nat Immunol 2004; 5: 1219–26.
- 49 Asselin-Paturel C, Trinchieri G. Production of type I interferons: plasmacytoid dendritic cells and beyond. J Exp Med 2005; 202: 461–5.
- 50 Watarai H, Sekine E, Inoue S, Nakagawa R, Kaisho T, Taniguchi M. PDC-TREM, a plasmacytoid dendritic cell-specific receptor, is responsible for augmented production of type I interferon. Proc Natl Acad Sci USA 2008; 105: 2993–8.
- 51 Liu YJ. IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu Rev Immunol 2005; 23: 275–306.
- 52 Chapman MD, Vailes LD, Hayden ML, Benjamin DC, Platts-Mills TA, Arruda LK. Structural and antigenic studies of cockroach allergens and their relevance to asthma. Adv Exp Med Biol 1996; 409: 95–101.
Citing Literature
